Progress of Type I Organic Photosensitizers for Photodynamic Therapy

Jie Zhang; Yonghui Pan; Chunxu He; Yuan Wang; Xiaofei Miao; Hui Zhao; Quli Fan; Wenbo Hu

doi:10.3788/CJL240454

[1] Xia C F, Dong X S, Li H et al. Cancer statistics in China and United States, 2022: profiles, trends, and determinants[J]. Chinese Medical Journal, 135, 584-590(2022).

[2] Yang Y, Zheng X, Chen L et al. Multifunctional gold nanoparticles in cancer diagnosis and treatment[J]. International Journal of Nanomedicine, 17, 2041-2067(2022).

[3] Fan W P, Yung B, Huang P et al. Nanotechnology for multimodal synergistic cancer therapy[J]. Chemical Reviews, 117, 13566-13638(2017).

[4] Xu K, Zhang T, Shao J J et al. Progress of glutathione-responsive photosensitizers for tumor therapy[J]. Chinese Journal of Lasers, 50, 0307202(2023).

[5] Almeida A, Faustino M A F, Tomé J P C. Photodynamic inactivation of bacteria: finding the effective targets[J]. Future Medicinal Chemistry, 7, 1221-1224(2015).

[6] Dolmans D E J G J, Fukumura D, Jain R K. Photodynamic therapy for cancer[J]. Nature Reviews Cancer, 3, 380-387(2003).

[7] Li X S, Lee S Y, Yoon J. Supramolecular photosensitizers rejuvenate photodynamic therapy[J]. Chemical Society Reviews, 47, 1174-1188(2018).

[8] Fan W P, Huang P, Chen X Y. Overcoming the Achilles’ heel of photodynamic therapy[J]. Chemical Society Reviews, 45, 6488-6519(2016).

[9] Foote C S. Definition of type I and type II photosensitized oxidation[J]. Photochemistry and Photobiology, 54, 659(1991).

[10] Wang S W, Lei M. Recent advances in two-photon excited photodynamic therapy[J]. Chinese Journal of Lasers, 49, 1507101(2022).

[11] Li B H, Chen T L, Lin L et al. Recent progress in photodynamic therapy: from fundamental research to clinical applications[J]. Chinese Journal of Lasers, 49, 0507101(2022).

[12] Tan L C, Shen X X, He Z Q et al. The role of photodynamic therapy in triggering cell death and facilitating antitumor immunology[J]. Frontiers in Oncology, 12, 863107(2022).

[13] Dang J J, He H, Chen D L et al. Manipulating tumor hypoxia toward enhanced photodynamic therapy (PDT)[J]. Biomaterials Science, 5, 1500-1511(2017).

[14] Dichiara M, Prezzavento O, Marrazzo A et al. Recent advances in drug discovery of phototherapeutic non-porphyrinic anticancer agents[J]. European Journal of Medicinal Chemistry, 142, 459-485(2017).

[15] Zhang Y, Zhao M, Miao J et al. Hemicyanine-based type I photosensitizers for antihypoxic activatable photodynamic therapy[J]. ACS Materials Letters, 5, 3058-3067(2023).

[16] Huang L, Zhao S J, Wu J S et al. Photodynamic therapy for hypoxic tumors: advances and perspectives[J]. Coordination Chemistry Reviews, 438, 213888(2021).

[17] Zhou Z J, Song J B, Nie L M et al. Reactive oxygen species generating systems meeting challenges of photodynamic cancer therapy[J]. Chemical Society Reviews, 45, 6597-6626(2016).

[18] Li X S, Kwon N, Guo T et al. Innovative strategies for hypoxic-tumor photodynamic therapy[J]. Angewandte Chemie, 57, 11522-11531(2018).

[19] Wang Y Y, Liu Y C, Sun H W et al. Type I photodynamic therapy by organic-inorganic hybrid materials: from strategies to applications[J]. Coordination Chemistry Reviews, 395, 46-62(2019).

[20] Yang B W, Chen Y, Shi J L. Reactive oxygen species (ROS)-based nanomedicine[J]. Chemical Reviews, 119, 4881-4985(2019).

[21] Cai Y, Si W L, Huang W et al. Organic dye based nanoparticles for cancer phototheranostics[J]. Small, 14, 1704247(2018).

[22] Yao T T, Wang J, Xue Y F et al. A photodynamic antibacterial spray-coating based on the host-guest immobilization of the photosensitizer methylene blue[J]. Journal of Materials Chemistry B, 7, 5089-5095(2019).

[23] Li M L, Xia J, Tian R S et al. Near-infrared light-initiated molecular superoxide radical generator: rejuvenating photodynamic therapy against hypoxic tumors[J]. Journal of the American Chemical Society, 140, 14851-14859(2018).

[24] Li M L, Xiong T, Du J J et al. Superoxide radical photogenerator with amplification effect: surmounting the Achilles' heels of photodynamic oncotherapy[J]. Journal of the American Chemical Society, 141, 2695-2702(2019).

[25] Li M L, Shao Y J, Kim J H et al. Unimolecular photodynamic O2-economizer to overcome hypoxia resistance in phototherapeutics[J]. Journal of the American Chemical Society, 142, 5380-5388(2020).

[26] Phillips M J, Voeltz G K. Structure and function of ER membrane contact sites with other organelles[J]. Nature Reviews: Molecular Cell Biology, 17, 69-82(2016).

[27] Li S M, Chen Y C, Wu Y P et al. An endoplasmic reticulum targeting type I photosensitizer for effective photodynamic therapy against hypoxic tumor cells[J]. Chemistry, 28, e202202680(2022).

[28] Kamkaew A, Lim S H, Lee H B et al. BODIPY dyes in photodynamic therapy[J]. Chemical Society Reviews, 42, 77-88(2013).

[29] Niu L Y, Guan Y S, Chen Y Z et al. BODIPY-based ratiometric fluorescent sensor for highly selective detection of glutathione over cysteine and homocysteine[J]. Journal of the American Chemical Society, 134, 18928-18931(2012).

[30] Turksoy A, Yildiz D, Akkaya E U. Photosensitization and controlled photosensitization with BODIPY dyes[J]. Coordination Chemistry Reviews, 379, 47-64(2019).

[31] Ye S Y, Rao J M, Qiu S H et al. Rational design of conjugated photosensitizers with controllable photoconversion for dually cooperative phototherapy[J]. Advanced Materials, 31, 1806346(2019).

[32] Byrne A T, O’Connor A E, Hall M et al. Vascular-targeted photodynamic therapy with BF2-chelated tetraaryl-azadipyrromethene agents: a multi-modality molecular imaging approach to therapeutic assessment[J]. British Journal of Cancer, 101, 1565-1573(2009).

[33] Gallagher W M, Allen L T, O’Shea C et al. A potent nonporphyrin class of photodynamic therapeutic agent: cellular localisation, cytotoxic potential and influence of hypoxia[J]. British Journal of Cancer, 92, 1702-1710(2005).

[34] Gorman A, Killoran J, O’Shea C et al. In vitro demonstration of the heavy-atom effect for photodynamic therapy[J]. Journal of the American Chemical Society, 126, 10619-10631(2004).

[35] Killoran J, Allen L, Gallagher J F et al. Synthesis of BF2 chelates of tetraarylazadipyrromethenes and evidence for their photodynamic therapeutic behaviour[J]. Chemical Communications, 1862-1863(2002).

[36] Wang J G, Hou Y J, Lei W H et al. DNA photocleavage by a cationic BODIPY dye through both singlet oxygen and hydroxyl radical: new insight into the photodynamic mechanism of BODIPYs[J]. ChemPhysChem, 13, 2739-2747(2012).

[37] Lai Y C, Chang C C. Photostable BODIPY-based molecule with simultaneous type I and type II photosensitization for selective photodynamic cancer therapy[J]. Journal of Materials Chemistry B, 2, 1576-1583(2014).

[38] Teng K X, Chen W K, Niu L Y et al. BODIPY-based photodynamic agents for exclusively generating superoxide radical over singlet oxygen[J]. Angewandte Chemie, 60, 19912-19920(2021).

[39] Teng K X, Niu L Y, Yang Q Z. A host-guest strategy for converting the photodynamic agents from a singlet oxygen generator to a superoxide radical generator[J]. Chemical Science, 13, 5951-5956(2022).

[40] Teng K X, Niu L Y, Yang Q Z. Supramolecular photosensitizer enables oxygen-independent generation of hydroxyl radicals for photodynamic therapy[J]. Journal of the American Chemical Society, 145, 4081-4087(2023).

[41] Chen D P, Wang Z C, Dai H M et al. Boosting O2•- photogeneration via promoting intersystem crossing and electron-donating efficiency of aza-BODIPY-based nanoplatforms for hypoxic-tumor photodynamic therapy[J]. Small Methods, 7, 2300889(2023).

[42] Chen D P, Yu Q, Huang X et al. A highly-efficient type I photosensitizer with robust vascular-disruption activity for hypoxic-and-metastatic tumor specific photodynamic therapy[J]. Small, 16, 2001059(2020).

[43] Wang L F, Qian Y. Modification of a SOCT-ISC type triphenylamine-BODIPY photosensitizer by a multipolar dendrimer design for photodynamic therapy and two-photon fluorescence imaging[J]. Biomaterials Science, 11, 1459-1469(2023).

[44] Nguyen V N, Qi S J, Kim S et al. An emerging molecular design approach to heavy-atom-free photosensitizers for enhanced photodynamic therapy under hypoxia[J]. Journal of the American Chemical Society, 141, 16243-16248(2019).

[45] Nguyen V N, Baek G, Qi S J et al. A lysosome-localized thionaphthalimide as a potential heavy-atom-free photosensitizer for selective photodynamic therapy[J]. Dyes and Pigments, 177, 108265(2020).

[46] Kobayashi H, Ogawa M, Alford R et al. New strategies for fluorescent probe design in medical diagnostic imaging[J]. Chemical Reviews, 110, 2620-2640(2010).

[47] Zhang X F, Zhang J L, Liu L M. Fluorescence properties of twenty fluorescein derivatives: lifetime, quantum yield, absorption and emission spectra[J]. Journal of Fluorescence, 24, 819-826(2014).

[48] An J, Tang S L, Hong G B et al. An unexpected strategy to alleviate hypoxia limitation of photodynamic therapy by biotinylation of photosensitizers[J]. Nature Communications, 13, 2225(2022).

[49] Chen W L, Wang Z H, Tian M Y et al. Integration of TADF photosensitizer as “electron pump” and BSA as “electron reservoir” for boosting type I photodynamic therapy[J]. Journal of the American Chemical Society, 145, 8130-8140(2023).

[50] Shigemitsu H, Ohkubo K, Sato K et al. Fluorescein-based type I supramolecular photosensitizer via induction of charge separation by self-assembly[J]. JACS Au, 2, 1472-1478(2022).

[51] Shigemitsu H, Sato K, Hagio S et al. Amphiphilic rhodamine nano-assembly as a type I supramolecular photosensitizer for photodynamic therapy[J]. ACS Applied Nano Materials, 5, 14954-14960(2022).

[52] Liu Y, Li X M, Niu X Y et al. In situ self-assembled biosupramolecular porphyrin nanofibers for enhancing photodynamic therapy in tumors[J]. Nanoscale, 12, 11119-11129(2020).

[53] Pham T C, Nguyen V N, Choi Y et al. Recent strategies to develop innovative photosensitizers for enhanced photodynamic therapy[J]. Chemical Reviews, 121, 13454-13619(2021).

[54] Wu M S, Liu Z Y, Zhang W A. An ultra-stable bio-inspired bacteriochlorin analogue for hypoxia-tolerant photodynamic therapy[J]. Chemical Science, 12, 1295-1301(2020).

[55] Cui L Y, Lin Q Y, Jin C S et al. A PEGylation-free biomimetic porphyrin nanoplatform for personalized cancer theranostics[J]. ACS Nano, 9, 4484-4495(2015).

[56] Luo T K, Ni K Y, Culbert A et al. Nanoscale metal-organic frameworks stabilize bacteriochlorins for type I and type II photodynamic therapy[J]. Journal of the American Chemical Society, 142, 7334-7339(2020).

[57] Yang Y, Wang L, Cao H Q et al. Photodynamic therapy with liposomes encapsulating photosensitizers with aggregation-induced emission[J]. Nano Letters, 19, 1821-1826(2019).

[58] Pucelik B, Sułek A, Drozd A et al. Enhanced cellular uptake and photodynamic effect with amphiphilic fluorinated porphyrins: the role of sulfoester groups and the nature of reactive oxygen species[J]. International Journal of Molecular Sciences, 21, 2786(2020).

[59] Sun H, Guo R H, Guo Y H et al. Boosting type-I and type-II ROS production of water-soluble porphyrin for efficient hypoxic tumor therapy[J]. Molecular Pharmaceutics, 20, 606-615(2023).

[60] Zhang H Y, Li W T, Tan G H et al. The anti-cancer potency of photodynamic therapy of a novel chlorin derivative Amidochlorin p6 (ACP)[J]. RSC Advances, 7, 40873-40880(2017).

[61] Wu M S, Chen C, Liu Z Y et al. Regulating the bacterial oxygen microenvironment via a perfluorocarbon-conjugated bacteriochlorin for enhanced photodynamic antibacterial efficacy[J]. Acta Biomaterialia, 142, 242-252(2022).

[62] Cheng J J, Zhao H T, Yao L et al. Simple and multifunctional natural self-assembled sterols with anticancer activity-mediated supramolecular photosensitizers for enhanced antitumor photodynamic therapy[J]. ACS Applied Materials & Interfaces, 11, 29498-29511(2019).

[63] Ke Z, Xie A Z, Chen J J et al. Naturally available hypericin undergoes electron transfer for type I photodynamic and photothermal synergistic therapy[J]. Biomaterials Science, 8, 2481-2487(2020).

[64] Li X W, Liu W M, Zheng X L et al. Lipid droplet targeting-guided hypoxic photodynamic therapy with curcumin analogs[J]. Chemical Communications, 59, 4181-4184(2023).

[65] Hu F, Xu S D, Liu B. Photosensitizers with aggregation-induced emission: materials and biomedical applications[J]. Advanced Materials, 30, 1801350(2018).

[66] Wang H P, Chen X, Qi Y L et al. Aggregation-induced emission (AIE)-guided dynamic assembly for disease imaging and therapy[J]. Advanced Drug Delivery Reviews, 179, 114028(2021).

[67] Wang Y B, Shi L L, Wu W B et al. Tumor-activated photosensitization and size transformation of nanodrugs[J]. Advanced Functional Materials, 31, 2010241(2021).

[68] Kenry, Liu B. Enhancing the theranostic performance of organic photosensitizers with aggregation-induced emission[J]. Accounts of Materials Research, 3, 721-734(2022).

[69] Yu Y W, Jia H Y, Liu Y B et al. Recent progress in type I aggregation-induced emission photosensitizers for photodynamic therapy[J]. Molecules, 28, 332(2022).

[70] Zhuang Z Y, Dai J, Yu M X et al. Type I photosensitizers based on phosphindole oxide for photodynamic therapy: apoptosis and autophagy induced by endoplasmic reticulum stress[J]. Chemical Science, 11, 3405-3417(2020).

[71] Wan Q, Zhang R Y, Zhuang Z Y et al. Molecular engineering to boost AIE-active free radical photogenerators and enable high-performance photodynamic therapy under hypoxia[J]. Advanced Functional Materials, 30, 2002057(2020).

[72] Zhao X X, Dai Y P, Ma F L et al. Molecular engineering to accelerate cancer cell discrimination and boost AIE-active type I photosensitizer for photodynamic therapy under hypoxia[J]. Chemical Engineering Journal, 410, 128133(2021).

[73] Chen K Q, He P, Wang Z M et al. A feasible strategy of fabricating type I photosensitizer for photodynamic therapy in cancer cells and pathogens[J]. ACS Nano, 15, 7735-7743(2021).

[74] Xiao P H, Shen Z P, Wang D L et al. Precise molecular engineering of type I photosensitizers with near-infrared aggregation-induced emission for image-guided photodynamic killing of multidrug-resistant bacteria[J]. Advanced Science, 9, 2104079(2022).

[75] Liu Z X, Wang Q, Qiu W S et al. AIE-active luminogens as highly efficient free-radical ROS photogenerator for image-guided photodynamic therapy[J]. Chemical Science, 13, 3599-3608(2022).

[76] Kang M M, Zhang Z J, Xu W H et al. Good steel used in the blade: well-tailored type-I photosensitizers with aggregation-induced emission characteristics for precise nuclear targeting photodynamic therapy[J]. Advanced Science, 8, 2100524(2021).

[77] Xiao Y F, Chen W C, Chen J X et al. Amplifying free radical generation of AIE photosensitizer with small singlet-triplet splitting for hypoxia-overcoming photodynamic therapy[J]. ACS Applied Materials & Interfaces, 14, 5112-5121(2022).

[78] Fang L P, Han M D, Zhang Y et al. Single component organic photosensitizer with NIR-I emission realizing type-I photodynamic and GSH-depletion caused ferroptosis synergistic theranostics[J]. Advanced Healthcare Materials, 12, 2300134(2023).

[79] Yan D Y, Xie W, Zhang J Y et al. Donor/π-bridge manipulation for constructing a stable NIR-II aggregation-induced emission luminogen with balanced phototheranostic performance[J]. Angewandte Chemie, 60, 26769-26776(2021).

[80] Li D, Chen X H, Wang D L et al. Synchronously boosting type-I photodynamic and photothermal efficacies via molecular manipulation for pancreatic cancer theranostics in the NIR-II window[J]. Biomaterials, 283, 121476(2022).

[81] Tian B, Wang C, Zhang S et al. Photothermally enhanced photodynamic therapy delivered by nano-graphene oxide[J]. ACS Nano, 5, 7000-7009(2011).

[82] Hu D H, Sheng Z H, Gao G H et al. Activatable albumin-photosensitizer nanoassemblies for triple-modal imaging and thermal-modulated photodynamic therapy of cancer[J]. Biomaterials, 93, 10-19(2016).

[83] Liang P P, Huang X Y, Wang Y et al. Tumor-microenvironment-responsive nanoconjugate for synergistic antivascular activity and phototherapy[J]. ACS Nano, 12, 11446-11457(2018).

[84] Wang Y F, Sun Y D, Ran J B et al. Utilization of nonradiative excited-state dissipation for promoted phototheranostics based on an AIE-active type I ROS generator[J]. ACS Applied Materials & Interfaces, 14, 225-235(2022).

[85] Guo J J, Dai J, Peng X L et al. 9, 10-phenanthrenequinone: a promising kernel to develop multifunctional antitumor systems for efficient type I photodynamic and photothermal synergistic therapy[J]. ACS Nano, 15, 20042-20055(2021).

[86] Lü S B, Liu Y H, Zhao Y L et al. Rational design of a small organic photosensitizer for NIR-I imaging-guided synergistic photodynamic and photothermal therapy[J]. Biomaterials Science, 10, 4785-4795(2022).

[87] Xiao P H, Xie W, Zhang J Y et al. De novo design of reversibly pH-switchable NIR-II aggregation-induced emission luminogens for efficient phototheranostics of patient-derived tumor xenografts[J]. Journal of the American Chemical Society, 145, 334-344(2023).

[88] Yu Y W, Wu S, Zhang L et al. Cationization to boost both type I and type II ROS generation for photodynamic therapy[J]. Biomaterials, 280, 121255(2022).

[89] Liu S S, Wang B N, Yu Y W et al. Cationization-enhanced type I and type II ROS generation for photodynamic treatment of drug-resistant bacteria[J]. ACS Nano, 16, 9130-9141(2022).

[90] Yu Y W, Liu Y B, Chen Y T et al. Cationic AIE-active photosensitizers for highly efficient photodynamic eradication of drug-resistant bacteria[J]. Materials Chemistry Frontiers, 7, 96-105(2023).

[91] Wu W B. High-performance conjugated polymer photosensitizers[J]. Chem, 4, 1762-1764(2018).

[92] Wu W B, Mao D, Xu S D et al. Polymerization-enhanced photosensitization[J]. Chem, 4, 1937-1951(2018).

[93] Hu L W, Chen Z K, Liu Y S et al. In vivo bioimaging and photodynamic therapy based on two-photon fluorescent conjugated polymers containing dibenzothiophene-S, S-dioxide derivatives[J]. ACS Applied Materials & Interfaces, 12, 57281-57289(2020).

[94] Liu S J, Zhang H K, Li Y Y et al. Strategies to enhance the photosensitization: polymerization and the donor-acceptor even-odd effect[J]. Angewandte Chemie, 130, 15409-15413(2018).

[95] Wang S W, Wu W B, Manghnani P et al. Polymerization-enhanced two-photon photosensitization for precise photodynamic therapy[J]. ACS Nano, 13, 3095-3105(2019).

[96] Wu W B, Liu B. Modulating the optical properties and functions of organic molecules through polymerization[J]. Materials Horizons, 9, 99-111(2022).

[97] Cheng J X, Zhou Y P, Xu S D et al. From main-chain conjugated polymer photosensitizer to hyperbranched polymer photosensitizer: expansion of the polymerization-enhanced photosensitization effect for photodynamic therapy[J]. Journal of Materials Chemistry B, 10, 5008-5015(2022).

[98] Li L Q, Shao C, Liu T et al. An NIR-II-emissive photosensitizer for hypoxia-tolerant photodynamic theranostics[J]. Advanced Materials, 32, 2003471(2020).

[99] Gu Y, Lai H J, Chen Z Y et al. Chlorination-mediated π–π stacking enhances the photodynamic properties of a NIR-II emitting photosensitizer with extended conjugation[J]. Angewandte Chemie, 62, e202303476(2023).

[100] Wen K K, Tan H, Peng Q et al. Achieving efficient NIR-II type-I photosensitizers for photodynamic/photothermal therapy upon regulating chalcogen elements[J]. Advanced Materials, 34, 2108146(2022).

[101] Wang Y, Li J G, Zhang Y K et al. Rational design of a meso phosphate-substituted pyronin as a type I photosensitizer for photodynamic therapy[J]. Chemical Communications, 58, 7797-7800(2022).

[102] Jiang Q Y, Li P X, Qiu J R et al. Lysosome-targeting phenalenones as efficient type I/II photosensitizers for anticancer photodynamic therapy[J]. European Journal of Medicinal Chemistry, 255, 115418(2023).

[103] Chen W, Zhang Y, Yi H B et al. Type I photosensitizer targeting G-quadruplex RNA elicits augmented immunity for cancer ablation[J]. Angewandte Chemie, 62, e202300162(2023).

[104] Juvekar V, Lim C S, Lee D J et al. An azo dye for photodynamic therapy that is activated selectively by two-photon excitation[J]. Chemical Science, 12, 427-434(2020).

[105] Lee D J, Juvekar V, Lee H W et al. Cancer-targeted azo dye for two-photon photodynamic therapy in human colon tissue[J]. Analytical Chemistry, 93, 16821-16827(2021).

[106] Zhao J, Huang R, Gao Y et al. Realizing near-infrared (NIR)-triggered type-I PDT and PTT by maximizing the electronic exchange energy of perylene diimide-based photosensitizers[J]. ACS Materials Letters, 5, 1752-1759(2023).