Porphyrin photosensitizers in photodynamic therapy and its applications

Kou, Jiayuan; Dou, Dou; Yang, Liming

doi:10.18632/oncotarget.20189

Cited by 422 publications

(339 citation statements)

References 101 publications

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“…To test how well these upfield CEST agents could be detected, we performed an in vivo study in live BALB/c mice bearing A549 cells‐derived xenografts. We administered 50 µL of a 0.1 M TPPS 4 solution, a known photosensitizer for photodynamic therapy, through intratumoral injection. CEST images were acquired before and after administration, revealing the distribution of TPPS 4 within the tumor.…”

Section: Resultsmentioning

confidence: 99%

Free‐base porphyrins as CEST MRI contrast agents with highly upfield shifted labile protons

Zhang

Yuan

et al. 2019

Magnetic Resonance in Med

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Purpose CEST has become a preeminent technology for the rapid detection and grading of tumors, securing its widespread use in both laboratory and clinical research. However, many existing CEST MRI agents exhibit a sensitivity limitation due to small chemical shifts between their exchangeable protons and water. We propose a new group of CEST MRI agents, free‐base porphyrins and chlorin, with large exchangeable proton chemical shifts from water for enhanced detection. Methods To test these newly identified CEST agents, we acquired a series of Z‐spectra at multiple pH values and saturation field strengths to determine their CEST properties. The data were analyzed using the quantifying exchange using saturation power method to quantify exchange rates. After identifying several promising candidates, a porphyrin solution was injected into tumor‐bearing mice, and MR images were acquired to assess detection feasibility in vivo. Results Based on the Z‐spectra, the inner nitrogen protons in free‐base porphyrins and chlorin resonate from −8 to −13.5 ppm from water, far shifted from the majority of endogenous metabolites (0‐4 ppm) and Nuclear Overhauser enhancements (−1 to −3.5 ppm) and far removed from the salicylates, imidazoles, and anthranillates (5‐12 ppm). The exchange rates are sufficiently slow to intermediate (500‐9000 s−1) to allow robust detection and were sensitive to substituents on the porphyrin ring. Conclusion These results highlight the capabilities of free‐base porphyrins and chlorin as highly upfield CEST MRI agents and provide a new scaffold that can be integrated into a variety of diagnostic or theranostic agents for biomedical applications.

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Section: Resultsmentioning

confidence: 99%

Free‐base porphyrins as CEST MRI contrast agents with highly upfield shifted labile protons

Zhang

Yuan

et al. 2019

Magnetic Resonance in Med

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“…Photodynamic therapy (PDT) is a noninvasive, clinically approved therapy used to treat a variety of cancers and non‐neoplastic diseases . It employs a small‐molecule photosensitiser (PS), light and endogenous molecular oxygen to produce cytotoxic reactive oxygen species (ROS) .…”

Section: Methodsmentioning

confidence: 99%

“…These PSs accumulate in cancer cells based on the enhanced permeability and retention (EPR) effect . As a result, selectivity in cancer cells over normal cells is modest, thus, adverse side effects are often observed in patients due to the destruction of surrounding healthy cells upon irradiation . To solve this issue, much work has focused on developing activatable photosensitisers (aPSs) whereby in addition to light, a cancer biomarker is also required for ROS and fluorescence production.…”

Section: Methodsmentioning

confidence: 99%

Exploiting the Cellular Redox‐Control System for Activatable Photodynamic Therapy

2019

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Photodynamic therapy (PDT) has been successfully used to treat a variety of cancers. However, one drawback has been the adverse side effects experienced by patients during therapy, as a result of the destruction of normal tissues upon irradiation. Herein, we describe the design, synthesis and characterisation of a photosensitiser to overcome this issue that, in addition to light, is also dependent on the overactive redox system present in cancer cells for its activation. Our probe consists of the photosensitiser, protoporphyrin IX, and a FRET‐based quencher dye, BHQ‐3, on a scaffold containing a disulfide bond. The close proximity of BHQ‐3 to protoporphyrin IX quenches its ability to fluoresce and produce reactive oxygen species, whereas nonenzymatic or enzymatic reduction can recover its native properties. We further demonstrate its ability to be activated in cancer cells in a thiol‐dependent manner and destroy breast and lung cancer cells upon red‐light irradiation.

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“…The photosensitisers that are used for PDT can be classified biochemically as first-, second-, and thirdgeneration photosensitisers. 37 The photosensitisers that were used in the studies were from the second generation with the exception of hypericin-laden nanoparticles, which was used in the study by Nafee et al 35 and which belong to the third-generation photosensitiser class. The second-generation photosensitiser that is most commonly used in recent times is 5-aminolevulinic acid.…”

Section: Photosensitizersmentioning

confidence: 99%

Antimicrobial photodynamic therapy in skin wound healing: A systematic review of animal studies

Sun

Ogawa

Xiao

et al. 2019

International Wound Journal

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Bacterial infection is a common wound complication that can significantly delay healing. Classical local therapies for infected wounds are expensive and are frequently ineffective. One alternative therapy is photodynamic therapy (PDT). We conducted a systematic review to clarify whether PDT is useful for bacteria‐infected wounds in animal models. PubMed and Medline were searched for articles on PDT in infected skin wounds in animals. The language was limited to English. Nineteen articles met the inclusion criteria. The overall study methodological quality was moderate, with a low‐moderate risk of bias. The animal models were mice and rats. The wounds were excisional, burn, and abrasion wounds. Wound size ranged from 6 mm in diameter to 1.5 × 1.5 cm2. Most studies inoculated the wounds with Pseudomonas aeruginosa or methicillin‐resistant Staphylococcus aureus. Eleven and 17 studies showed that the PDT of infected wounds significantly decreased wound size and bacterial counts, respectively. Six, four, and two studies examined the effect of PDT on infected wound‐cytokine levels, wound‐healing time, and body weight, respectively. Most indicated that PDT had beneficial effects on these variables. PDT accelerated bacteria‐infected wound healing in animals by promoting wound closure and killing bacteria.

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Porphyrin photosensitizers in photodynamic therapy and its applications

Cited by 422 publications

References 101 publications

Free‐base porphyrins as CEST MRI contrast agents with highly upfield shifted labile protons

Free‐base porphyrins as CEST MRI contrast agents with highly upfield shifted labile protons

Exploiting the Cellular Redox‐Control System for Activatable Photodynamic Therapy

Antimicrobial photodynamic therapy in skin wound healing: A systematic review of animal studies

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