Medicine › Pulmonary and Respiratory Medicine

Photodynamic Therapy Research Studies

Description

This cluster of papers focuses on the application of photodynamic therapy (PDT) in oncology and microbiology. It covers topics such as cancer treatment, photosensitizers, singlet oxygen, antimicrobial PDT, nanoparticles, tumor imaging, cell death pathways, and reactive oxygen species. The papers discuss the mechanisms, clinical applications, and future directions of PDT in treating cancer and localized infections.

Keywords

Photodynamic Therapy; Cancer Treatment; Photosensitizers; Singlet Oxygen; Antimicrobial; Nanoparticles; Tumor Imaging; Cell Death Pathways; Reactive Oxygen Species; Clinical Applications

BACKGROUND Photodynamic therapy (PDT) for cancer patients has developed into an important new clinical treatment modality in the past 25 years. PDT involves administration of a tumor-localizing photosensitizer or photosensitizer … BACKGROUND Photodynamic therapy (PDT) for cancer patients has developed into an important new clinical treatment modality in the past 25 years. PDT involves administration of a tumor-localizing photosensitizer or photosensitizer prodrug (5-aminolevulinic acid [ALA], a precursor in the heme biosynthetic pathway) and the subsequent activation of the photosensitizer by light. Although several photosensitizers other than ALA-derived protoporphyrin IX (PpIX) have been used in clinical PDT, ALA-based PDT has been the most active area of clinical PDT research during the past 5 years. Studies have shown that a higher accumulation of ALA-derived PpIX in rapidly proliferating cells may provide a biologic rationale for clinical use of ALA-based PDT and diagnosis. However, no review updating the clinical data has appeared so far. METHODS A review of recently published data on clinical ALA-based PDT and diagnosis was conducted. RESULTS Several individual studies in which patients with primary nonmelanoma cutaneous tumors received topical ALA-based PDT have reported promising results, including outstanding cosmetic results. However, the modality with present protocols does not, in general, appear to be superior to conventional therapies with respect to initial complete response rates and long term recurrence rates, particularly in the treatment of nodular skin tumors. Topical ALA-PDT does have the following advantages over conventional treatments: it is noninvasive; it produces excellent cosmetic results; it is well tolerated by patients; it can be used to treat multiple superficial lesions in short treatment sessions; it can be applied to patients who refuse surgery or have pacemakers and bleeding tendency; it can be used to treat lesions in specific locations, such as the oral mucosa or the genital area; it can be used as a palliative treatment; and it can be applied repeatedly without cumulative toxicity. Topical ALA-PDT also has potential as a treatment for nonneoplastic skin diseases. Systemic administration of ALA does not seem to be severely toxic, but the advantage of using this approach for PDT of superficial lesions of internal hollow organs is still uncertain. The ALA-derived porphyrin fluorescence technique would be useful in the diagnosis of superficial lesions of internal hollow organs. CONCLUSIONS Promising results of ALA-based clinical PDT and diagnosis have been obtained. The modality has advantages over conventional treatments. However, some improvements need to be made, such as optimization of parameters of ALA-based PDT and diagnosis; increased tumor selectivity of ALA-derived PpIX; better understanding of light distribution in tissue; improvement of light dosimetry procedure; and development of simpler, cheaper, and more efficient light delivery systems. Cancer 1997; 79:2282-308. Ā© 1997 American Cancer Society.
Whereas the photodynamic therapy (PDT) of cancer has recently shown rapid clinical acceptance, photodynamic antimicrobial chemotherapy (PACT)--which predates the related cancer regimen--is not widely appreciated. Like PDT, PACT utilizes photosensitizers … Whereas the photodynamic therapy (PDT) of cancer has recently shown rapid clinical acceptance, photodynamic antimicrobial chemotherapy (PACT)--which predates the related cancer regimen--is not widely appreciated. Like PDT, PACT utilizes photosensitizers and visible or ultraviolet light in order to give a phototoxic response, normally via oxidative damage. Currently, the major use of PACT is in the disinfection of blood products, particularly for viral inactivation, although more clinically-based protocols are being developed, e.g. in the treatment of oral infection. The technique has been shown to be effective in vitro against bacteria (including drug-resistant strains), yeasts, viruses and parasites. A wide range of photosensitizers, both natural and synthetic, is available with differing physicochemical make-up and light-absorption properties. PACT is proposed as a potential, low-cost approach to the treatment of locally occurring infection.
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMetal Complexes as Photo- and RadiosensitizersHasrat Ali and Johan E. van LierView Author Information MRC Group in the Radiation Sciences, Department of Nuclear Medicine and Radiobiology, Faculty … ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMetal Complexes as Photo- and RadiosensitizersHasrat Ali and Johan E. van LierView Author Information MRC Group in the Radiation Sciences, Department of Nuclear Medicine and Radiobiology, Faculty of Medicine, UniversitĆ© de Sherbrooke, Sherbrooke, QuĆ©bec, Canada J1H 5N4 Cite this: Chem. Rev. 1999, 99, 9, 2379–2450Publication Date (Web):August 14, 1999Publication History Received2 March 1999Revised5 July 1999Published online14 August 1999Published inissue 8 September 1999https://pubs.acs.org/doi/10.1021/cr980439yhttps://doi.org/10.1021/cr980439yresearch-articleACS PublicationsCopyright Ā© 1999 American Chemical SocietyRequest reuse permissionsArticle Views5952Altmetric-Citations767LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Dyes and pigments,Ligands,Pyrroles,Reaction products,Tumors Get e-Alerts
Quenching of excited singlet and triplet states of many substances by ground state molecular oxygen produces singlet oxygen, the lowest electronically excited singlet state of molecular oxygen, O2(1Ī”g). The fractions … Quenching of excited singlet and triplet states of many substances by ground state molecular oxygen produces singlet oxygen, the lowest electronically excited singlet state of molecular oxygen, O2(1Ī”g). The fractions of singlet and triplet states quenched which produce singlet oxygen and the quantum yields of formation of singlet oxgyen in fluid solutions have been critically compiled. Methods for determination yield parameters have been reviewed. Data have been compiled from the literature through 1991. Photosensitizers such as aromatic hydrocarbons, aromatic ketones and thiones, quinones, coumarins, fluoresceins, transition metal complexes, and heterocyclics are included in Table 1. Porphyrins and phthalocyanines are included in Table 2. Other materials which have been investigated for singlet oxygen production, such as dyes and drugs, are collected in Table 3 along with heterogeneous systems such as polymer-bound photosensitizers.
Photodynamic therapy (PDT) uses light-activated drugs to treat diseases ranging from cancer to age-related macular degeneration and antibiotic-resistant infections. This paper reviews the current status of PDT with an emphasis … Photodynamic therapy (PDT) uses light-activated drugs to treat diseases ranging from cancer to age-related macular degeneration and antibiotic-resistant infections. This paper reviews the current status of PDT with an emphasis on the contributions of physics, biophysics and technology, and the challenges remaining in the optimization and adoption of this treatment modality. A theme of the review is the complexity of PDT dosimetry due to the dynamic nature of the three essential components -- light, photosensitizer and oxygen. Considerable progress has been made in understanding the problem and in developing instruments to measure all three, so that optimization of individual PDT treatments is becoming a feasible target. The final section of the review introduces some new frontiers of research including low dose rate (metronomic) PDT, two-photon PDT, activatable PDT molecular beacons and nanoparticle-based PDT.
A novel nanoparticle-based drug carrier for photodynamic therapy is reported which can provide stable aqueous dispersion of hydrophobic photosensitizers, yet preserve the key step of photogeneration of singlet oxygen, necessary … A novel nanoparticle-based drug carrier for photodynamic therapy is reported which can provide stable aqueous dispersion of hydrophobic photosensitizers, yet preserve the key step of photogeneration of singlet oxygen, necessary for photodynamic action. A multidisciplinary approach is utilized which involves (i) nanochemistry in micellar cavity to produce these carriers, (ii) spectroscopy to confirm singlet oxygen production, and (iii) in vitro studies using tumor cells to investigate drugāˆ’carrier uptake and destruction of cancer cells by photodynamic action. Ultrafine organically modified silica-based nanoparticles (diameter ∼30 nm), entrapping water-insoluble photosensitizing anticancer drug 2-devinyl-2-(1-hexyloxyethyl) pyropheophorbide, have been synthesized in the nonpolar core of micelles by hydrolysis of triethoxyvinylsilane. The resulting drug-doped nanoparticles are spherical, highly monodispersed, and stable in aqueous system. The entrapped drug is more fluorescent in aqueous medium than the free drug, permitting use of fluorescence bioimaging studies. Irradiation of the photosensitizing drug entrapped in nanoparticles with light of suitable wavelength results in efficient generation of singlet oxygen, which is made possible by the inherent porosity of the nanoparticles. In vitro studies have demonstrated the active uptake of drug-doped nanoparticles into the cytosol of tumor cells. Significant damage to such impregnated tumor cells was observed upon irradiation with light of wavelength 650 nm. Thus, the potential of using ceramic-based nanoparticles as drug carriers for photodynamic therapy has been demonstrated.
Photodynamic therapy (PDT) is an emerging treatment modality for a range of disease classes, both cancerous and noncancerous. This has brought about an active pursuit of new PDT agents that … Photodynamic therapy (PDT) is an emerging treatment modality for a range of disease classes, both cancerous and noncancerous. This has brought about an active pursuit of new PDT agents that can be optimized for the unique set of photophysical characteristics that are required for a successful clinical agent. We now describe a totally new class of PDT agent, the BF2-chelated 3,5-diaryl-1H-pyrrol-2-yl-3,5-diarylpyrrol-2-ylideneamines (tetraarylazadipyrromethenes). Optimized synthetic procedures have been developed to facilitate the generation of an array of specifically substituted derivatives to demonstrate how control of key therapeutic parameters such as wavelength of maximum absorbance and singlet-oxygen generation can be achieved. Photosensitizer absorption maxima can be varied within the body's therapeutic window between 650 and 700 nm, with high extinction coefficients ranging from 75 000 to 85 000 M-1 cm-1. Photosensitizer singlet-oxygen generation level was modulated by the exploitation of the heavy-atom effect. An array of photosensitizers with and without bromine atom substituents gave rise to a series of compounds with varying singlet-oxygen generation profiles. X-ray structural evidence indicates that the substitution of the bromine atoms has not caused a planarity distortion of the photosensitizer. Comparative singlet-oxygen production levels of each photosensitizer versus two standards demonstrated a modulating effect on singlet-oxygen generation depending upon substituent patterns about the photosensitizer. Confocal laser scanning microscopy imaging of 18a in HeLa cervical carcinoma cells proved that the photosensitizer was exclusively localized to the cellular cytoplasm. In vitro light-induced toxicity assays in HeLa cervical carcinoma and MRC5-SV40 transformed fibroblast cancer cell lines confirmed that the heavy-atom effect is viable in a live cellular system and that it can be exploited to modulate assay efficacy. Direct comparison of the efficacy of the photosensitizers 18b and 19b, which only differ in molecular structure by the presence of two bromine atoms, illustrated an increase in efficacy of more than a 1000-fold in both cell lines. All photosensitizers have very low to nondeterminable dark toxicity in our assay system.
Singlet oxygen, O2(a1Ī”g), the lowest excited electronic state of molecular oxygen, has been known to the scientific community for ∼80 years. It has a characteristic chemistry that sets it apart … Singlet oxygen, O2(a1Ī”g), the lowest excited electronic state of molecular oxygen, has been known to the scientific community for ∼80 years. It has a characteristic chemistry that sets it apart from the triplet ground state of molecular oxygen, O2(X3Ī£āˆ’g), and is important in fields that range from atmospheric chemistry and materials science to biology and medicine. For such a ā€œmature citizenā€, singlet oxygen nevertheless remains at the cutting-edge of modern science. In this critical review, recent work on singlet oxygen is summarized, focusing primarily on systems that involve light. It is clear that there is indeed still something new under the sun (243 references).
The first page of this article is displayed as the abstract. The first page of this article is displayed as the abstract.
Singlet oxygen, a metastable state of normal triplet oxygen, has been identified as the cytotoxic agent that is probably responsible for in vitro inactivation of TA-3 mouse mammary carcinoma cells … Singlet oxygen, a metastable state of normal triplet oxygen, has been identified as the cytotoxic agent that is probably responsible for in vitro inactivation of TA-3 mouse mammary carcinoma cells following incorporation of hematoporphyrin and exposure to red light. This photodynamic inactivation can be completely inhibited by intracellular 1,3-diphenylisobenzofuran. This very efficient singlet oxygen trap is not toxic to the cells nor does it absorb the light responsible for hematoporphyrin activation. We have found that the singlet oxygen-trapping product, o-dibenzoylbenzene, is formed nearly quantitatively intracellularly when both the furan and hematoporphyrin are present during illumination but not when only the furan is present during illumination. The protective effect against photodynamic inactivation of the TA-3 cells afforded by 1,3-diphenylisobenzofuran coupled with the nearly quantitative formation of the singlet oxygen-trapping product indicates that singlet oxygen is the probable agent responsible for toxicity in this system.
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPhysical Mechanisms of Generation and Deactivation of Singlet OxygenClaude Schweitzer and Reinhard SchmidtView Author Information Institut für Physikalische und Theoretische Chemie, Johann Wolfgang Goethe-UniversitƤt, Marie-Curie-Strasse 11, D60439 … ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPhysical Mechanisms of Generation and Deactivation of Singlet OxygenClaude Schweitzer and Reinhard SchmidtView Author Information Institut für Physikalische und Theoretische Chemie, Johann Wolfgang Goethe-UniversitƤt, Marie-Curie-Strasse 11, D60439 Frankfurt am Main, Germany Cite this: Chem. Rev. 2003, 103, 5, 1685–1758Publication Date (Web):April 30, 2003Publication History Received6 September 2002Published online30 April 2003Published inissue 1 May 2003https://pubs.acs.org/doi/10.1021/cr010371dhttps://doi.org/10.1021/cr010371dresearch-articleACS PublicationsCopyright Ā© 2003 American Chemical SocietyRequest reuse permissionsArticle Views22577Altmetric-Citations1756LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Aromatic compounds,Hydrocarbons,Kinetic parameters,Quenching,Solvents Get e-Alerts
ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTImaging and Photodynamic Therapy: Mechanisms, Monitoring, and OptimizationJonathan P. Celli†, Bryan Q. Spring†, Imran Rizvi†—, Conor L. Evans†, Kimberley S. Samkoe—, Sarika Verma†, Brian W. Pogue†—, and … ADVERTISEMENT RETURN TO ISSUEPREVReviewNEXTImaging and Photodynamic Therapy: Mechanisms, Monitoring, and OptimizationJonathan P. Celli†, Bryan Q. Spring†, Imran Rizvi†—, Conor L. Evans†, Kimberley S. Samkoe—, Sarika Verma†, Brian W. Pogue†—, and Tayyaba Hasan*†View Author Information Wellman Center for Photomedicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, and Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire 03755* To whom correspondence should be addressed. E-mail: [email protected]†Massachusetts General Hospital and Harvard Medical School.—Dartmouth College.Cite this: Chem. Rev. 2010, 110, 5, 2795–2838Publication Date (Web):March 30, 2010Publication History Received4 September 2009Published online30 March 2010Published inissue 12 May 2010https://pubs.acs.org/doi/10.1021/cr900300phttps://doi.org/10.1021/cr900300preview-articleACS PublicationsCopyright Ā© 2010 American Chemical SocietyRequest reuse permissionsArticle Views23102Altmetric-Citations1936LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Biological imaging,Cancer,Fluorescence,Fluorescence imaging,Tumors Get e-Alerts
Administration of hematoporphyrin derivative i.v. followed by local exposure to red light has resulted in complete or partial response in 111 of 113 cutaneous or s.c. malignant lesions. Tumors treated … Administration of hematoporphyrin derivative i.v. followed by local exposure to red light has resulted in complete or partial response in 111 of 113 cutaneous or s.c. malignant lesions. Tumors treated have included carcinomas of the breast, colon, prostate, squamous cell, basal cell, and endometrium; malignant melanoma; mycosis fungoides; chondrosarcoma; and angiosarcoma. No type has been found to be unresponsive. In several cases complete clearing of chest wall metastatis has been achieved in treated areas. Deep-seated and pigmented tumors required a higher dose of drug for effective treatment than did the more superficial and nonpigmented lesions. A high therapeutic ratio between tumor and skin response has been obtained by allowing at least 3 days between drug injection and exposure to the therapeutic light for 2,5-mg/kg doses and at least a 4-day interval for 5.0-mg/kg doses.
Abstract Photodynamic therapy (PDT) is now a well‐recognized modality for the treatment of cancer. While PDT has developed progressively over the last century, great advances have been observed in the … Abstract Photodynamic therapy (PDT) is now a well‐recognized modality for the treatment of cancer. While PDT has developed progressively over the last century, great advances have been observed in the field in recent years. The concept of dual selectivity of PDT agents is now widely accepted due to the relative specificity and selectivity of PDT along with the absence of harmful side effects often encountered with chemotherapy or radiotherapy. Traditionally, porphyrin‐based photosensitizers have dominated the PDT field but these first generation photosensitizers have several disadvantages, with poor light absorption and cutaneous photosensitivity being the predominant side effects. As a result, the requirement for new photosensitizers, including second generation porphyrins and porphyrin derivatives as well as third generation photosensitizers has arisen, with the aim of alleviating the problems encountered with first generation porphyrins and improving the efficacy of PDT. The investigation of nonporphyrin photosensitizers for the development of novel PDT agents has been considerably less extensive than porphyrin‐based compounds; however, structural modification of nonporphyrin photosensitizers has allowed for manipulation of the photochemotherapeutic properties. The aim of this review is to provide an insight into PDT photosensitizers clinically approved for application in oncology, as well as those which show significant potential in ongoing preclinical studies.
Photodynamic therapy (PDT) is a clinically approved, minimally invasive therapeutic procedure that can exert a selective cytotoxic activity toward malignant cells. The procedure involves administration of a photosensitizing agent followed … Photodynamic therapy (PDT) is a clinically approved, minimally invasive therapeutic procedure that can exert a selective cytotoxic activity toward malignant cells. The procedure involves administration of a photosensitizing agent followed by irradiation at a wavelength corresponding to an absorbance band of the sensitizer. In the presence of oxygen, a series of events lead to direct tumor cell death, damage to the microvasculature, and induction of a local inflammatory reaction. Clinical studies revealed that PDT can be curative, particularly in early stage tumors. It can prolong survival in patients with inoperable cancers and significantly improve quality of life. Minimal normal tissue toxicity, negligible systemic effects, greatly reduced long-term morbidity, lack of intrinsic or acquired resistance mechanisms, and excellent cosmetic as well as organ function-sparing effects of this treatment make it a valuable therapeutic option for combination treatments. With a number of recent technological improvements, PDT has the potential to become integrated into the mainstream of cancer treatment.
In recent years several review articles and books have been published on the use of porphyrin-based compounds in photodynamic therapy (PDT). This critical review is focused on (i) the basic … In recent years several review articles and books have been published on the use of porphyrin-based compounds in photodynamic therapy (PDT). This critical review is focused on (i) the basic concept of PDT, (ii) advantages of long-wavelength absorbing photosensitizers (PS), (iii) a brief discussion on recent advances in developing PDT agents, and (iv) the various synthetic strategies designed at the Roswell Park Cancer Institute, Buffalo, for developing highly effective long-wavelength PDT agents and their utility in constructing the conjugates with tumor-imaging and therapeutic potential (Theranostics). The clinical status of certain selected PDT agents is also summarized (205 references).
Photodynamic therapy (PDT) has received increased attention since the regulatory approvals have been granted to several photosensitizing drugs and light applicators worldwide. Much progress has been seen in basic sciences … Photodynamic therapy (PDT) has received increased attention since the regulatory approvals have been granted to several photosensitizing drugs and light applicators worldwide. Much progress has been seen in basic sciences and clinical photodynamics in recent years. This review will focus on new developments of clinical investigation and discuss the usefulness of various forms of PDT techniques for curative or palliative treatment of malignant and non-malignant diseases.
Photodynamic therapy (PDT), also known as photoradiation therapy, phototherapy, or photochemo-therapy, involves the use of a photoactive dye (photosensitizer) that is activated by exposure to light of a specific wavelength … Photodynamic therapy (PDT), also known as photoradiation therapy, phototherapy, or photochemo-therapy, involves the use of a photoactive dye (photosensitizer) that is activated by exposure to light of a specific wavelength in the presence of oxygen. The transfer of energy from the activated photosensitizer to available oxygen results in the formation of toxic oxygen species, such as singlet oxygen and free radicals. These very reactive chemical species can damage proteins, lipids, nucleic acids, and other cellular components. Applications of PDT in dentistry are growing rapidly: the treatment of oral cancer, bacterial and fungal infection therapies, and the photodynamic diagnosis (PDD) of the malignant transformation of oral lesions. PDT has shown potential in the treatment of oral leukoplakia, oral lichen planus, and head and neck cancer. Photodynamic antimicrobial chemotherapy (PACT) has been efficacious in the treatment of bacterial, fungal, parasitic, and viral infections. The absence of genotoxic and mutagenic effects of PDT is an important factor for long-term safety during treatment. PDT also represents a novel therapeutic approach in the management of oral biofilms. Disruption of plaque structure has important consequences for homeostasis within the biofilm. Studies are now leading toward selective photosensitizers, since killing the entire flora leaves patients open to opportunistic infections. Dentists deal with oral infections on a regular basis. The oral cavity is especially suitable for PACT, because it is relatively accessible to illumination.
Photodynamic therapy (PDT) was discovered more than 100 years ago, and has since become a well-studied therapy for cancer and various non-malignant diseases including infections. PDT uses photosensitizers (PSs, non-toxic … Photodynamic therapy (PDT) was discovered more than 100 years ago, and has since become a well-studied therapy for cancer and various non-malignant diseases including infections. PDT uses photosensitizers (PSs, non-toxic dyes) that are activated by absorption of visible light to initially form the excited singlet state, followed by transition to the long-lived excited triplet state. This triplet state can undergo photochemical reactions in the presence of oxygen to form reactive oxygen species (including singlet oxygen) that can destroy cancer cells, pathogenic microbes and unwanted tissue. The dual-specificity of PDT relies on accumulation of the PS in diseased tissue and also on localized light delivery. Tetrapyrrole structures such as porphyrins, chlorins, bacteriochlorins and phthalocyanines with appropriate functionalization have been widely investigated in PDT, and several compounds have received clinical approval. Other molecular structures including the synthetic dyes classes as phenothiazinium, squaraine and BODIPY (boron-dipyrromethene), transition metal complexes, and natural products such as hypericin, riboflavin and curcumin have been investigated. Targeted PDT uses PSs conjugated to antibodies, peptides, proteins and other ligands with specific cellular receptors. Nanotechnology has made a significant contribution to PDT, giving rise to approaches such as nanoparticle delivery, fullerene-based PSs, titania photocatalysis, and the use of upconverting nanoparticles to increase light penetration into tissue. Future directions include photochemical internalization, genetically encoded protein PSs, theranostics, two-photon absorption PDT, and sonodynamic therapy using ultrasound.
This review summarizes the latest progress in deep photodynamic therapy (PDT), which overcomes the Achilles' heel of PDT. This review summarizes the latest progress in deep photodynamic therapy (PDT), which overcomes the Achilles' heel of PDT.
Photodynamic therapy (PDT) is a clinically approved cancer therapy, based on a photochemical reaction between a light activatable molecule or photosensitizer, light, and molecular oxygen. When these three harmless components … Photodynamic therapy (PDT) is a clinically approved cancer therapy, based on a photochemical reaction between a light activatable molecule or photosensitizer, light, and molecular oxygen. When these three harmless components are present together, reactive oxygen species are formed. These can directly damage cells and/or vasculature, and induce inflammatory and immune responses. PDT is a two-stage procedure, which starts with photosensitizer administration followed by a locally directed light exposure, with the aim of confined tumor destruction. Since its regulatory approval, over 30 years ago, PDT has been the subject of numerous studies and has proven to be an effective form of cancer therapy. This review provides an overview of the clinical trials conducted over the last 10 years, illustrating how PDT is applied in the clinic today. Furthermore, examples from ongoing clinical trials and the most recent preclinical studies are presented, to show the directions, in which PDT is headed, in the near and distant future. Despite the clinical success reported, PDT is still currently underutilized in the clinic. We also discuss the factors that hamper the exploration of this effective therapy and what should be changed to render it a more effective and more widely available option for patients.
ADVERTISEMENT RETURN TO ISSUEPerspectiveNEXTCurrent Clinical and Preclinical Photosensitizers for Use in Photodynamic TherapyMichael R. Detty, Scott L. Gibson, and Stephen J. WagnerView Author Information Department of Chemistry, University at Buffalo, … ADVERTISEMENT RETURN TO ISSUEPerspectiveNEXTCurrent Clinical and Preclinical Photosensitizers for Use in Photodynamic TherapyMichael R. Detty, Scott L. Gibson, and Stephen J. WagnerView Author Information Department of Chemistry, University at Buffalo, The State University of New York, Buffalo, New York 14260-3000, Department of Biochemistry and Biophysics, University of Rochester Medical Center, 601 Elmwood Avenue, Box 607, Rochester, New York 14642, and Blood & Cell Therapy Development, American Red Cross Holland Laboratory, Rockville, Maryland 20855 Cite this: J. Med. Chem. 2004, 47, 16, 3897–3915Publication Date (Web):June 19, 2004Publication History Received30 March 2004Published online19 June 2004Published inissue 1 July 2004https://pubs.acs.org/doi/10.1021/jm040074bhttps://doi.org/10.1021/jm040074breview-articleACS PublicationsCopyright Ā© 2004 American Chemical SocietyRequest reuse permissionsArticle Views7608Altmetric-Citations909LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Light,Molecules,Oxygen,Photodynamic therapy,Photosensitization Get e-Alerts
Photodynamic therapy (PDT) is a ground breaking medical technique which uses lasers to activate light-sensitive chemicals to treat cancer and other diseases without resorting to surgery. For the first time, … Photodynamic therapy (PDT) is a ground breaking medical technique which uses lasers to activate light-sensitive chemicals to treat cancer and other diseases without resorting to surgery. For the first time, Chemical Aspects of Photodynamic Therapy introduces in an accessible way the physics, chemistry and biology behind the technique. This highly a
Photodynamic therapy involves administration of a tumorlocalizing photosensitizing agent, which may require metabolic synthesis (i.e., a prodrug), followed by activation of the agent by light of a specific wavelength. This … Photodynamic therapy involves administration of a tumorlocalizing photosensitizing agent, which may require metabolic synthesis (i.e., a prodrug), followed by activation of the agent by light of a specific wavelength. This therapy results in a sequence of photochemical and photobiologic processes that cause irreversible photodamage to tumor tissues. Results from preclinical and clinical studies conducted worldwide over a 25-year period have established photodynamic therapy as a useful treatment approach for some cancers. Since 1993, regulatory approval for photodynamic therapy involving use of a partially purified, commercially available hematoporphyrin derivative compound (PhotofrinĀ®) in patients with early and advanced stage cancer of the lung, digestive tract, and genitourinary tract has been obtained in Canada, The Netherlands, France, Germany, Japan, and the United States. We have attempted to conduct and present a comprehensive review of this rapidly expanding field. Mechanisms of subcellular and tumor localization of photosensitizing agents, as well as of molecular, cellular, and tumor responses associated with photodynamic therapy, are discussed. Technical issues regarding light dosimetry are also considered. [J Natl Cancer Inst 1998;90:889-905]
Escherichia coli lysate-based cell-free systems have gained traction for a variety of point-of-use biological applications. Lysate-based cell-free reactions can be freeze-dried, deployed without requiring cold chain, and have a high … Escherichia coli lysate-based cell-free systems have gained traction for a variety of point-of-use biological applications. Lysate-based cell-free reactions can be freeze-dried, deployed without requiring cold chain, and have a high ease of use through simple rehydration. To maximize their potential, it is of interest to stabilize these reactions to withstand a variety of conditions for long-term storage and use, including stabilization to UV exposure. To address this issue and aid in point-of-use applications, we investigate the use of synthetic melanin nanoparticles as UV-protective additives that are compatible with cell-free reactions. These particles have broadband absorption properties and radical scavenging activity that allow for protection from free radical generation during prolonged UV exposure. Stabilizing cell-free reactions in this way may prolong the stability for use in the field where exposure to sunlight is inevitable.
Double-loaded liposomes are a system in which a drug is incorporated in the vesicle lipid layers after aqueous phase inclusion complexation to form a drug-in-cyclodextrin-in phospholipid vesicles complex. Umbelliferone (UMB) … Double-loaded liposomes are a system in which a drug is incorporated in the vesicle lipid layers after aqueous phase inclusion complexation to form a drug-in-cyclodextrin-in phospholipid vesicles complex. Umbelliferone (UMB) is a naturally occurring coumarin used as a photoactive agent because of its UV light absorption ability. In this study, the double loading (DL) technique was used to encapsulate ā€œUMB in hydroxy propyl-β-cyclodextrin (HP-β-CD)-in-liposomes (UMB-CDLP)ā€. This led to the creation of ā€œdouble-loaded liposomes encasing UMB in HP-β-CD (DL-UMB-CDLP)ā€, specifically developed to combine the power of solubilisation of HP-β-CD with the sustained release characteristics of phospholipid vesicles to improve solubility and dissolution profile. HP-β-CD and UMB inclusion complexes prepared by different methods were characterized by FTIR spectroscopy, DSC, saturation solubility, x-ray diffractometry, and scanning electron microscopy. DL-UMB-CDLP was developed using a thin film/lipid hydration method and a Box-Behnken design and was assessed by TEM, in-vitro diffusion studies and biological evaluation. The optimized DL-UMB-CDLP formulation demonstrated promising results, indicating the development of a stable composition. Animals treated with the DL-UMB-CDLP gel and exposed to the immediate irradiation protocol proved the UMB’s ability to protect against UV-induced oxidative damage based on the amount of antioxidant enzymes estimated to be present in rat skin.
M. Sato , On Hasegawa , Michihide Kono +6 more | International Journal of Oral and Maxillofacial Surgery
A BSTRACT Introduction: ā€œOral squamous cell carcinoma (OSCC)ā€ is one of the most common malignancies of the oral cavity, often requiring aggressive surgical intervention. ā€œPhotodynamic therapy (PDT)ā€ has emerged as … A BSTRACT Introduction: ā€œOral squamous cell carcinoma (OSCC)ā€ is one of the most common malignancies of the oral cavity, often requiring aggressive surgical intervention. ā€œPhotodynamic therapy (PDT)ā€ has emerged as a minimally invasive treatment option to enhance the efficacy of surgical treatments. The combination of PDT with surgery has been suggested to reduce recurrence rates and improve overall outcomes. Methods: This research aims to evaluate the efficacy of PDT as an adjunct to surgery in treating OSCC, using three key parameters: tumor recurrence rates, survival outcomes, and postoperative complications. A cohort of OSCC patients treated with surgery alone was compared with a cohort treated with both surgery and PDT. Results: Patients treated with surgery and PDT demonstrated significantly lower tumor recurrence rates ( P < 0.05) and improved 3-year survival outcomes ( P < 0.01) compared to surgery alone. Postoperative complication rates did not differ significantly between the two groups (P > 0.05). Conclusion: PDT as an adjunct to surgery shows promise in improving recurrence rates and survival outcomes in OSCC without increasing postoperative complications. Further large-scale studies are needed to confirm these findings.
ABSTRACT Introduction Diabetic foot ulcers affect approximately 15% of individuals with diabetes, compromising their quality of life and placing an additional burden on the public health system. Objectives This study … ABSTRACT Introduction Diabetic foot ulcers affect approximately 15% of individuals with diabetes, compromising their quality of life and placing an additional burden on the public health system. Objectives This study aims to evaluate the effects of the antimicrobial photodynamic therapy (aPDT) in tissue repair through the analysis of two case studies involving individuals with diabetes‐related foot lesions. Methods aPDT was performed using 1% methylene blue, a cluster of four red lasers (660 nm) with an average radiant power of 100 mW, and radiant energy per emitter of 6 J. The exposure time was 1 min, resulting in a total radiant energy per session of 24 J. Patients were evaluated on sessions 1, 3, 5, 10, and 30 days after the completion of treatment. Results Using the Bates‐Jensen Wound Assessment Tool (BWAT) scale as a tool to assess wound progression, Patient 1 had an initial score of 37 points, which reduced to 24 points by the end of treatment, resulting in a decrease of 13 points on the scale. Patient 2 started with 36 points and finished with 14 points, achieving complete healing. Conclusions Treatment led to improved wound quality, evidenced by a reduction in BWAT scores, a 74.9% decrease in wound area in patient 1 with consistent healing progress, and complete wound closure in patient 2. Although limited by its case‐series design, this study contributes preliminary clinical evidence suggesting the potential benefits of antimicrobial photodynamic therapy (aPDT) in the management of diabetic foot ulcers and highlights the need for larger, controlled trials to validate its efficacy. In conclusion, aPDT was effective across all evaluated outcomes in these two reported cases. Trial Registration NCT06416462 (initial release: 09/23).
Photodynamic therapy is a non-invasive treatment strategy for various types of cancer, based on the use of light to activate a photosensitizer which triggers processes leading to cell death. Given … Photodynamic therapy is a non-invasive treatment strategy for various types of cancer, based on the use of light to activate a photosensitizer which triggers processes leading to cell death. Given the increasing interest in the development of mitochondria-targeted photosensitizers, in this study we synthesized two novel thiadiazol-substituted porphyrins, 5,10,15,20-tetra(2,1,3-benzothiadiazol-5-yl) porphyrin (C1) and 5,10,15,20-tetra(1,2,3-thiadiazol-4-yl) porphyrin (C2), designed to target mitochondria in cancer cells thanks to the azole residues present in their structure. The two porphyrinic compounds were characterized in terms of structural and photophysical properties, revealing high yields of singlet oxygen production. Their interaction with biological structures was analyzed in a triple-negative human breast carcinoma cell line (MDA-MB-231), either as free compounds or delivered via mitochondriotropic liposome formulations. Both newly synthesized porphyrins entered MDA-MB-231 cells, with compound C2 demonstrating more efficient localization in the cytoplasm and in mitochondria. Dark and phototoxicity tests were also performed: both compounds proved to be effective phototoxic agents, with C2 showing the highest activity, making it a promising photosensitizer for mitochondria-targeted photodynamic therapy.
<title>Abstract</title> This study explored the in vitro potential of Aloe emodin (AE)-mediated antimicrobial photodynamic therapy (aPDT) against the emerging multidrug-resistant fungus <italic>Candida auris</italic>. While AE alone showed no significant antifungal … <title>Abstract</title> This study explored the in vitro potential of Aloe emodin (AE)-mediated antimicrobial photodynamic therapy (aPDT) against the emerging multidrug-resistant fungus <italic>Candida auris</italic>. While AE alone showed no significant antifungal activity, its activation with visible light (400–780 nm) at 10 µM resulted in a complete (100%) reduction of viable <italic>C. auris</italic> colony counts after 15 minutes of exposure. Conversely, the dark control group exhibited only a 30% decrease. Furthermore, AE-aPDT demonstrated a notable capacity to inhibit the initial development of <italic>C. auris</italic> biofilms. These findings highlight the potential of visible light-activated AE as an effective antimicrobial strategy against this resistant pathogen and its biofilms. The rapid and complete eradication of <italic>C. auris</italic> under these conditions suggests a promising avenue for developing disinfection protocols and potential therapeutic interventions against this critical global health threat.
Levofloxacin is an antibiotic classified as an emerging contaminant. Its presence in aquatic environments represents potential risks to ecosystems and human health, making its removal during wastewater treatment of relevant … Levofloxacin is an antibiotic classified as an emerging contaminant. Its presence in aquatic environments represents potential risks to ecosystems and human health, making its removal during wastewater treatment of relevant importance. Here, we present a comprehensive kinetic analysis of levofloxacin photodegradation under UVB solar irradiation, with emphasis on the influence of pH and dissolved oxygen, two conditions that can vary widely in wastewater and impact treatment efficiency. We also investigated the formation and role of reactive oxygen species in the degradation mechanism, as well as the cytotoxicity and antibacterial activity of photoproducts. Our findings reveal that the efficiency of levofloxacin photodegradation is highly dependent on environmental conditions; it requires neutral or slightly alkaline pH and a high concentration of dissolved oxygen, a situation not always observed in contaminated waters. Several reactive oxygen species are generated, with singlet oxygen being the most reactive with the antibiotic. We report for the first time the singlet oxygen quantum yield from levofloxacin. Bioassays demonstrated that photoproducts neither exhibit antibacterial activity nor induce significant cytotoxicity. Our study suggests that UVB treatment of contaminated effluent containing levofloxacin could be an effective and environmentally safe strategy for the antibiotic degradation under certain conditions of pH and dissolved oxygen.
Abstract Background 5‑Aminolevulinic acid (5-ALA) is a keto-carbon amino acid frequently used in glioma surgery for fluorescence-guided resection. Additionally, cytotoxic properties of 5‑ALA can be induced via stimulation with laser … Abstract Background 5‑Aminolevulinic acid (5-ALA) is a keto-carbon amino acid frequently used in glioma surgery for fluorescence-guided resection. Additionally, cytotoxic properties of 5‑ALA can be induced via stimulation with laser light in photodynamic therapy (PDT). Preclinical in vitro and in vivo trials have also demonstrated this effect to be inducible by photon irradiation as used in radiation treatment. This makes 5‑ALA a potential sensitizer for radiation therapy whose capabilities and limitations have not yet been fully evaluated. In this article, we present results from a systematic literature review regarding the evidence of 5‑ALA’s radiosensitizing properties and the context of its use. We discuss these findings in terms of the underlying mechanisms, their limitations, and the questions to be addressed in future clinical trials. Methods A systematic review in the PubMed database was performed via a specifically designed search term, including all search results that featured the combination of 5‑ALA with ionizing radiation. The last date of search was November 13, 2024. Risk of bias among study data was assessed individually according to the study setup after full-text analysis. The results were synthesized based on the underlying tumor entity. Results A total of 31 articles were included that examined the combination of 5‑ALA with radiotherapy (RT) in glioma ( n = 12), melanoma ( n = 6), breast ( n = 3), lung ( n = 2), prostate ( n = 4), and colorectal ( n = 1) cancer as well as in sarcoma ( n = 2) and primary CNS lymphoma ( n = 1). The radiosensitizing effect of 5‑ALA varies among these entities, with glioma and melanoma presenting the strongest body of evidence. Conclusion These results imply a basis for 5‑ALA as a possible radiosensitizer for RT, but several questions remain unanswered, as limitations arise from the fact that data are predominantly based on in vitro or rodent in vivo trials, with only two ongoing clinical trials and one case report involving human patients. Moreover, trial setups varied in terms of ALA dose and application timing.
Oral squamous cell carcinoma is still a global health issue, even if oral cavity is an easily accessible anatomical site, the diagnosis is still delayed. Conventional treatments, like chemotherapy and … Oral squamous cell carcinoma is still a global health issue, even if oral cavity is an easily accessible anatomical site, the diagnosis is still delayed. Conventional treatments, like chemotherapy and radiotherapy, are usually employed, but not without complications. These drawbacks have necessitated the need for new therapies, one of these is photodynamic therapy (PDT). Nanotechnologies-enhanced PDT has significantly improved tumor targeting, bioavailability, and light absorption, paving the way for its application in early-stage of oral squamous cell carcinoma (OSCC) and as part of combination therapies for advanced cases. Despite the potential advantages of PDT, such as tumor selectivity, minimization of systemic side effects and repeatability of treatment, some limitations still restrict its clinical application. Despite these challenges, its application in oral squamous cell carcinoma and oral potentially malignant disease is promising, both alone or in combination with other therapies. Addressing such pros and cons of this technique, PDT may then be a possible adjuvant tool in the management of OSCC.
Radiotherapy is the standard treatment for nearly 60 % of cancer patients. Despite advancements such as brachytherapy, stereotactic radiotherapy, and intensity-modulated radiotherapy, further improvements in efficacy and safety are needed. … Radiotherapy is the standard treatment for nearly 60 % of cancer patients. Despite advancements such as brachytherapy, stereotactic radiotherapy, and intensity-modulated radiotherapy, further improvements in efficacy and safety are needed. Radiodynamic therapy (RDT) is gaining attention, in which improved radiotherapy outcomes are achieved with the use of porphyrins such as protoporphyrin IX, verteporfin, Mn-porphyrins, and other porphyrinoids such as phthalocyanines and texaphyrins. While the light-based excitation mechanisms of these photosensitizing agents are widely established, their radiosensitization mechanisms remain unclear and underinvestigated. A comprehensive investigation into the observed physicochemical and biological effects of these compounds during radiotherapy enables the identification of several key underlying mechanisms to explain the radiocatalytic properties of porphyrins and porphyrin-related compounds. Porphyrin-like sensitizers can (1) be excited by Cherenkov radiation, (2) be ionized by secondary electrons, (3) initiate redox cycling reactions and enhance reactive oxygen species production, and (4) interfere with critical signaling pathways. These effects may synergistically combine to enhance the effects of ionizing radiation and boost the radiosensitivity of cancer cells, offering a powerful new direction for cancer treatment.
Candida auris is a fungal pathogen with frequent development of multidrug-resistance or pan-drug resistance. Currently, the treatment options for Candida auris are limited. Therefore, there is an urgent need for … Candida auris is a fungal pathogen with frequent development of multidrug-resistance or pan-drug resistance. Currently, the treatment options for Candida auris are limited. Therefore, there is an urgent need for alternative therapeutic strategies. Antimicrobial photodynamic therapy (aPDT), which generates reactive oxygen species (ROS) through light-activated photosensitizers, has shown promise against C. auris; however, its molecular mechanism remains unclear. To investigate COP1T-HA-mediated PDT-induced genomic alterations, we constructed a 3D genome map of Candida species, which uncovered the reorganization of chromatin architecture in response to PDT treatment. Our data showed that low-dose PDT causes subtle local adjustments in chromatin topology, whereas high-dose PDT leads to more pronounced changes in A/B compartmentalization, topologically associating domain (TAD) organization, and chromatin looping associated with key genes related to mitochondrial energy metabolism. Confocal imaging confirmed that high-dose COP1T-HA-mediated PDT induces localized ROS accumulation near the nucleus and a temporally ordered cellular stress response. Furthermore, functional validation through QCR10, NDUFA5, and MP knockouts confirmed the essential roles of these genes in mitochondrial integrity, ATP synthesis, ROS homeostasis, and biofilm formation. Mutants showed altered mitochondrial membrane potential, intracellular pH imbalance, and enhanced glycolytic compensation, highlighting the impact of electron transport disruption on energy metabolism. This study provides the first comprehensive insight into COP1T-HA-mediated PDT-induced chromatin reorganization in C. auris and establishes a direct connection between 3D genome remodeling and fungal energy metabolism, offering a foundation for chromatin-targeted antifungal strategies.
Type‐I photodynamic agents can not only produce cytotoxic reactive oxygen species, but also directly damage biomolecules through electron/hydrogen transfer process, exhibiting reduced dependence on oxygen concentration in photodynamic therapy (PDT). … Type‐I photodynamic agents can not only produce cytotoxic reactive oxygen species, but also directly damage biomolecules through electron/hydrogen transfer process, exhibiting reduced dependence on oxygen concentration in photodynamic therapy (PDT). The rational design of Type‐I photodynamic agents has attracted increasing attention. This minireview provides a comprehensive overview of Type‐I PDT and its advantages in treating hypoxic tumors. It systematically outlines two complementary design strategies: (i) thermodynamic modulation through molecular engineering to block the Type‐II energy transfer pathway, and (ii) kinetic enhancement of electron/hydrogen transfer to favor the Type‐I mechanism. Finally, key challenges in Type‐I PDT are discussed, and future perspectives are highlighted to facilitate the clinical translation of Type‐I photodynamic agents. We hope this review will stimulate further progress in the development of innovative PDT.
Abstract Axillary lymph node (ALN) status serves as a crucial prognostic indicator in breast cancer (BC). Currently, sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND) are the … Abstract Axillary lymph node (ALN) status serves as a crucial prognostic indicator in breast cancer (BC). Currently, sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND) are the standard methods for predicting and evaluating ALN status; however, intraoperative frozen section and pathological analysis are both time-consuming and laborious, and there is a certain false-positive rate. Therefore, there is a need for a method that can rapidly and accurately assess the status of ALN metastasis (ALNM) during surgery. To address the above clinical needs, this study combined near-infrared fluorescence imaging technology during BC surgery with advanced deep learning strategies to build a predictive model called "Multi-modal Fluorescence Imaging Feature Fusion Prediction" (MFI-FFP). For the multi-modal imaging data obtained during BC surgery, including white light imaging (WLI), near-infrared fluorescence imaging (FI), and pseudo-color imaging (PCI), we selectively customized feature extraction networks for each imaging modality to fully explore and utilized the complementary information between different modalities. We designed a multi-modal feature fusion module that effectively integrates features extracted from each modality by combining global and local information. Additionally, due to the common issues of class imbalance and classification challenges in real-world clinical datasets, we also designed a novel loss function to enhance the recognition of minority class instances. Through the above design, MFI-FFP can quickly and accurately determine the positive or negative of ALNM in surgery, reducing diagnostic time and costs, and ultimately improving patient outcomes. The BC lymph node image database used in this study was derived from intraoperative fluorescence videos of 93 patients. During the surgical procedure, 312 excised lymph nodes were obtained from these 93 patients. with 35 lymph nodes testing positive for metastasis. The ratio of negative samples to positive samples was approximately 8:1. During data preprocessing, key frames of each lymph node in the videos were captured and extracted as intraoperative fluorescence images. Each captured frame contained the three modes of data which include WLI, FI, and PCI. A total of 936 imaging data were captured, with 312 images corresponding to each mode. Experimental evaluations demonstrated that the MFI-FFP model achieved remarkable performance in predicting ALNM, with an area under the ROC curve (AUC) of 0.7512 and an accuracy (ACC) of 0.8617, significantly outperforming single-modality models (WLI: AUC 0.5810; FI: AUC 0.5226; PCI: AUC 0.5601) and dual-modality models (WLI+FI: AUC 0.6786; FI+PCI: AUC 0.6089; WLI+PCI: AUC 0.6571). Given the absence of dedicated multimodal models for intraoperative fluorescence data from BC lymph nodes, we concatenated multi-modal features and input them into models that excel in natural image classification tasks, including resnet18, swin_transformer, convNeXt, efficientnet_v2, mobilenet_v3. Experimental results indicated that our model significantly outperforms the best-performing model in natural image classification, MobileNet_v3, with an AUC value of 0.6595. This study not only validated the precision and reliability of the MFI-FFP model in predicting the status of ALNM in BC but also highlighted its substantial potential in assisting clinical decision-making and enabling real-time diagnosis of ALNM. Citation Format: He Sun, Xiaobo Zhu, Jiaqian Li, Zhenyu Liu, Yu An, Jie Tian. Prediction of Axillary Lymph Node Metastasis in Breast Cancer using Intraoperative Fluorescence Multi-modal Imaging [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P2-02-20.
Type‐I photodynamic agents can not only produce cytotoxic reactive oxygen species, but also directly damage biomolecules through electron/hydrogen transfer process, exhibiting reduced dependence on oxygen concentration in photodynamic therapy (PDT). … Type‐I photodynamic agents can not only produce cytotoxic reactive oxygen species, but also directly damage biomolecules through electron/hydrogen transfer process, exhibiting reduced dependence on oxygen concentration in photodynamic therapy (PDT). The rational design of Type‐I photodynamic agents has attracted increasing attention. This minireview provides a comprehensive overview of Type‐I PDT and its advantages in treating hypoxic tumors. It systematically outlines two complementary design strategies: (i) thermodynamic modulation through molecular engineering to block the Type‐II energy transfer pathway, and (ii) kinetic enhancement of electron/hydrogen transfer to favor the Type‐I mechanism. Finally, key challenges in Type‐I PDT are discussed, and future perspectives are highlighted to facilitate the clinical translation of Type‐I photodynamic agents. We hope this review will stimulate further progress in the development of innovative PDT.
Photodynamic therapy (PDT) is a minimally invasive treatment in which an external light source activates an injected photosensitizer (PS) to generate reactive oxygen species, causing localized cell death. Although the … Photodynamic therapy (PDT) is a minimally invasive treatment in which an external light source activates an injected photosensitizer (PS) to generate reactive oxygen species, causing localized cell death. Although the first PDT received FDA approval in 1995, clinical adoption has been limited, in part due to the limited tumor selectivity of PSs. The goal of this study was to develop a PS with improved tumor selectivity by incorporating a targeting peptide that selectively binds to the integrin αvβ6. The integrin αvβ6 is an epithelial-specific cell-surface receptor that is overexpressed in several cancer types, with expression level often linked to poor overall survival. The integrin αvβ6 targeting peptide (ABM-5G) was conjugated onto a water-soluble PS (IRDye700DX, IR700) in solution phase, and the resulting PS-αvβ6-targeted-peptide conjugate (IR700-ABM-5G, 1) demonstrated excellent photochemical and photophysical properties, including high extinction coefficient and singlet oxygen productivity similar to the nontargeted PS (free IR700). In vitro, 1 showed αvβ6-selective binding to and internalization into DX3puroβ6 (αvβ6+) cells vs DX3puro (αvβ6-) cells, and αvβ6-selective phototoxicity with EC50s of 1.6 nM for DX3puroβ6 cells and ≄ 250 nM for DX3puro cells. In mice bearing paired DX3puroβ6 (αvβ6+) and DX3puro (αvβ6-) tumor xenografts, the fluorescence intensity of 1 in DX3puroβ6 (αvβ6+) tumors was 2.5- to 7-fold higher than that of the other tissues (including DX3puro (αvβ6-) tumors, p < 0.0001), except for the kidneys and stomach. A single treatment of 1 (1.4 nmol per mouse) combined with near-infrared light exposure significantly suppressed the growth of DX3puroβ6 (αvβ6+) tumors (198 ± 112 mm3 vs 714 ± 251 mm3 for saline control, p < 0.0001, on day 37 post treatment). In summary, PDT treatment with 1 demonstrated αvβ6-selective therapeutic efficacy both in vitro and in vivo and is a promising targeted therapy for the treatment of a range of αvβ6-expressing cancers.
Abstract Tumormicroenvironment (TME) is a complex milieu of multiple cell types mainly including tumor cells, immune cells, endothelial cells and stromal cells. Immune cell profile within the TME can determine … Abstract Tumormicroenvironment (TME) is a complex milieu of multiple cell types mainly including tumor cells, immune cells, endothelial cells and stromal cells. Immune cell profile within the TME can determine success of immunotherapies, indicate therapeutic efficacy and determine any potential therapeutic toxicity in various malignancies including breast cancer. Spatially interrogating these immune cells is crucial in studying immune-immune and immune-tumor interactions. Characterizing immune cells require assessing cell marker expression using protein detection and activation markers using RNA detection. To address this, we have developed a high throughput RNAscopeā„¢ assay on the BOND RX to spatially visualize RNA and protein markers on the same slide. We utilized the new RNAscopeā„¢ Multiomic LS assay that can detect up to 6 RNA and protein targets in breast cancer FFPE tissue. The TSA-based amplification strategy offers signal boost for both RNA and protein targets. To optimize protein detection, the workflow is completely protease-free there by preserving antigen integrity and tissue morphology. The assay can be customized to include any target RNA and proteins of interest. Here, we demonstrate the use of our pre-conjugated antibody panel which includes CD8, CD4, FoxP3 and PanCK to visualize tumor infiltrating lymphocytes (TILs). We also utilized unconjugated primary antibodies for CD68 and CD163 to detect tumor macrophages in multiple tumor tissues. Infiltrating Cytotoxic T cell lymphocytes were detected using CD8, GZMB and IFNG co-expression. Regulatory T cells were detected using CD4, FOXP3 co-expression. PanCK was used as a tumor marker to delineate tumor from stroma. Similarly, tumor associated macrophages were detected using CD163, CD68 , IL10 and IL-1B expression. We also identified distinct M1 and M2 macrophage populations in the breast tumor sample. Citation Format: Anushka Dikshit, Debia Wakhloo, Julia Yu, Paul Liu, Sonali Deshpande. Spatial mulitomic assay for assessing immune cell phenotype and function in the tumor microenvironment [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P3-06-19.
To address the clinical challenges posed by symbiotic drug-resistant bacterial infections and tumor microenvironments, this study designed and synthesized novel carbazole/benzindole-based photosensitizers A1–A4, systematically evaluating their antitumor and antibacterial therapeutic … To address the clinical challenges posed by symbiotic drug-resistant bacterial infections and tumor microenvironments, this study designed and synthesized novel carbazole/benzindole-based photosensitizers A1–A4, systematically evaluating their antitumor and antibacterial therapeutic potential through chemo-photodynamic therapy. Especially, compound A4 demonstrated potent Type I/II reactive oxygen species (ROS) generation capabilities. In vitro experiments revealed that A4 concentration-dependently inhibited HT-29 cells under hypoxic conditions (IC50 = 0.89 μM) with a prominent photodynamic index (PI &gt; 9.23), and substantially promoted cancer cell programmed death. In antibacterial evaluations, A4 achieved the complete eradication of dermal MRSA infections within 7 days through ROS-mediated membrane disruption under illumination. In the HT-29 xenograft model, the PDT–chemotherapy synergy strategy achieved a tumor suppression rate of 96%. This work establishes an innovative strategy for the combinatorial management of multidrug-resistant infections and solid tumors.
Oral candidiasis, commonly caused by Candida (C.) albicans and other non-albicans Candida species, increases resistance to conventional antifungal therapies. This study aimed to evaluate the in vitro efficacy of antimicrobial … Oral candidiasis, commonly caused by Candida (C.) albicans and other non-albicans Candida species, increases resistance to conventional antifungal therapies. This study aimed to evaluate the in vitro efficacy of antimicrobial photodynamic therapy (aPDT) using a 450 nm diode laser in combination with curcumin and riboflavin against Candida spp. and Staphylococcus (S.) aureus. Reference strains of C. albicans, C. glabrata, C. krusei, and S. aureus were exposed to aPDT under varying incubation times and laser parameters, then viable microorganism cells (CFU) counts were assessed the microbial reduction, and statistical analyses were performed to evaluate significance. aPDT significantly reduced microbial viability in a time- and dose-dependent manner. Optimal incubation times were 20 min for Candida spp. and 10 min for S. aureus, with the highest efficacy observed at 400 mW and 120 s irradiation. The photosensitizer or laser alone had no significant antimicrobial effect. Curcumin/riboflavin-mediated aPDT is a promising alternative or adjunctive approach to conventional antimicrobial therapy, particularly for resistant oral infections.
Photodynamic therapy (PDT) was first demonstrated in 1903 by Von Tappeiner and Jesionek, combining light therapy with a photosensitizer and oxygen [...] Photodynamic therapy (PDT) was first demonstrated in 1903 by Von Tappeiner and Jesionek, combining light therapy with a photosensitizer and oxygen [...]
Abstract Peri‐implantitis is an inflammatory disease triggered by a dysbiotic biofilm on dental implants, leading to bone loss and potential implant failure. Although nonsurgical and surgical treatments can reduce the … Abstract Peri‐implantitis is an inflammatory disease triggered by a dysbiotic biofilm on dental implants, leading to bone loss and potential implant failure. Although nonsurgical and surgical treatments can reduce the inflammatory process, the high prevalence of peri‐implantitis suggests that these interventions are not always effective in arresting disease progression. This has prompted increased interest in antimicrobial photodynamic therapy (aPDT), which utilizes photosensitizers (PSs) activated by light to target bacterial infections. Despite promising benefits, aPDT has not yet achieved consistently favorable clinical outcomes. It may be due to the limitations of current PSs, including restricted light activation, insufficient tissue penetration, and variable antimicrobial efficacy. Additionally, the stability and selectivity of PSs are crucial for their effectiveness against pathogenic bacteria. Variations in light delivery systems and treatment protocols may also contribute to inconsistent results across studies. This review will address the clinical challenges of aPDT for peri‐implantitis, critically analyzing the shortcomings outlined in existing literature. It will further explore the chemical and biological mechanisms of PSs, providing insight into the underlying causes of clinical limitations. Finally, we will discuss potential improvements in PS compounds and treatment protocols that could enhance the therapeutic potential of aPDT, offering new perspectives on its role in managing peri‐implantitis.
A BSTRACT Aim: The purpose of this study was to compare the microbiological and clinical effects of antimicrobial photodynamic therapy (aPDT) in treating chronic periodontitis by using indocyanine green (ICG) … A BSTRACT Aim: The purpose of this study was to compare the microbiological and clinical effects of antimicrobial photodynamic therapy (aPDT) in treating chronic periodontitis by using indocyanine green (ICG) with an 810 nm diode laser and methylene blue (MB) with a 660 nm diode laser as adjuncts to scaling and root planing (SRP). Materials and Procedures: In this split-mouth design research, 14 people were recruited. Three sets of treatment sites were randomly assigned: SRP with aPDT utilizing MB or ICG (test groups) and SRP alone (control group). Using real-time polymerase chain reaction (RT-PCR), samples of subgingival plaque were examined for Tannerella forsythia, Porphyromonas gingivalis, and Treponema denticola. Microbiological counts and clinical indicators, such as Russell’s Periodontal Index (RI), Gingival Index (GI), Plaque Index (PI), clinical attachment loss (CAL), and probing depth (PD), were measured at baseline and three months later. Findings: When compared to the control sites, test sites treated with aPDT showed statistically significant improvements in both clinical and microbiological parameters ( P &lt; 0.001). Conclusion: MB and ICG photosensitizers combined with antimicrobial photodynamic therapy show great promise as an adjuvant treatment for chronic periodontitis.
Photodynamic therapy (PDT), a photochemical treatment modality centered on photosensitizers, is increasingly demonstrating its significant value in treating malignant tumors and microbial infections. Phthalocyanine compounds, as outstanding representatives of traditional … Photodynamic therapy (PDT), a photochemical treatment modality centered on photosensitizers, is increasingly demonstrating its significant value in treating malignant tumors and microbial infections. Phthalocyanine compounds, as outstanding representatives of traditional photosensitizers, have attracted considerable attention due to their excellent photophysical and photochemical properties. However, the hydrophobicity of their macrocyclic aromatic planes often leads to intermolecular aggregation, reducing reactive oxygen species (ROS) generation efficiency and impairing drug bioavailability. To address this limitation, carboxylation of the phthalocyanine ring periphery provides amidation sites, facilitating further functionalization and enabling combination with diverse materials, thereby expanding the application potential of phthalocyanine photosensitizers. Additionally, carboxyl substitution enhances the biocompatibility of phthalocyanine photosensitizers and helps mitigate the aggregation problem caused by their hydrophobic nature. Modification strategies for carboxyl-substituted phthalocyanines span multiple fields, including organic chemistry, biomacromolecules, polymeric materials, and inorganic nanomaterials. Based on our team's research, this review delves into the advances in preparation techniques and delivery systems for carboxyl-substituted phthalocyanine photosensitizers and their derivatives. It comprehensively analyzes their advantages and challenges in PDT and imaging systems, aiming to provide technical support and novel perspectives for the development and application of this class of photosensitizers, promote the advancement of PDT in fields such as malignant tumor and microbial infection treatment, drive innovation and application of related technologies, and offer more effective means and strategies for addressing clinical challenges.
Ultra-low locally advanced rectal cancer presents significant challenges for sphincter-preserving surgery due to its anatomical constraints and limited response to conventional neoadjuvant therapies. This case report describes a patient diagnosed … Ultra-low locally advanced rectal cancer presents significant challenges for sphincter-preserving surgery due to its anatomical constraints and limited response to conventional neoadjuvant therapies. This case report describes a patient diagnosed with stage IIIb (cT3N2M0) ultra-low rectal cancer who had a strong preference for sphincter preservation. Given the suboptimal efficacy of standard treatments in achieving sufficient tumor downstaging, a comprehensive 6-month neoadjuvant regimen was implemented, combining photodynamic therapy (PDT), chemotherapy, targeted therapy, and immunotherapy. PDT selectively induced tumor necrosis, disrupted the tumor vasculature, enhanced therapeutic agent penetration, and transformed the tumor microenvironment into an immune-responsive state. This multimodal approach resulted in significant tumor regression, facilitating sphincter-preserving radical resection. Postoperative pathological examination confirmed a pathological complete response, and the patient remains disease-free, with a progression-free survival exceeding 48 months. This case highlights the potential of a multimodal treatment approach, combining PDT with systemic therapies, to enhance tumor downstaging, potentiate the efficacy of immunotherapy, and improve sphincter preservation rates in ultra-low locally advanced rectal cancer. This integrated strategy offers a promising approach for optimizing clinical outcomes in these challenging cases.