Photodynamic therapy (PDT) is an advanced treatment method extensively used in oncology and other medical fields due to its ability to selectively destroy pathological cells. PDT operates through the activation of photosensitizers (PS) by light of a specific wavelength, resulting in the formation of reactive oxygen species (ROS) that cause cellular damage. PDT can be classified into three main approaches: tumor-targeted PDT, vascular-targeted PDT, and antimicrobial PDT. In oncology, PDT is predominantly used to target cancer cells while minimizing damage to healthy tissues. Additionally, PDT has shown promise in the diagnosis and treatment of bladder tumors, expanding its role in urological oncology. The mechanism of PDT in prostate cancer highlights its ability to target tumor vasculature, inducing ischemic necrosis while preserving surrounding tissues. The evolution of photosensitizers, particularly in prostate cancer, has led to second-generation compounds that offer faster, more efficient treatments with fewer side effects.
AlvarezNSevillaA. Current advances in photodynamic therapy (PDT) and the future potential of PDT-combinatorial cancer therapies. Int. J. Mol. Sci2024; 25: 1023.
NogueiraLTraceyATAlvimR, et al.Developments in vascular-targeted photodynamic therapy for urologic malignancies. Molecules2020; 25: 5417.
4.
JaoYDingSJChenCC. Antimicrobial photodynamic therapy for the treatment of oral infections: a systematic review. J Dent Sci2023; 18: 1453–1466.
5.
FlegarLBuerkBProschmannR, et al.Vascular-targeted photodynamic therapy in unilateral low-risk prostate cancer in Germany: 2-yr single-centre experience in a real-world setting compared with radical prostatectomy. Eur Urol Focus2022; 8: 121–127.
6.
AebisherDSerafinIBatóg-SzczęchK, et al.Photodynamic therapy in the treatment of cancer-the selection of synthetic photosensitizers. Pharmaceuticals (Basel2024; 17: 32.
7.
AbrahamseHHamblinMR. New photosensitizers for photodynamic therapy. Biochem J2016; 473: 347–364.
8.
KorotkovaISakhnoT. Nanoparticles with the aggregation-induced emission effect: properties and applications: photosensitizers for photodynamic therapy. Saarbrücken: LAP LAMBERT Academic Publishing, 2020, pp.1–93.
9.
OlszowyMNowak-PerlakMWoźniakM. Current strategies in photodynamic therapy (PDT) and photodynamic diagnostics (PDD) and the future potential of nanotechnology in cancer treatment. Pharmaceutics2023; 15: 1712.
10.
MinaevBFYashchukLB. Possible electronic mechanisms of generation and quenching of luminescence of singlet oxygen in the course of photodynamic therapy: ab initio study. Biopolym. Cell2006; 22: 231–235.
11.
MinaevB. Magnetic properties of reactive oxygen Species and their possible role in cancer therapy. Arch Cancer Sci Ther2024; 8: 048–053.
12.
BregnhøjMWestbergMMinaevBF, et al.Singlet oxygen photophysics in liquid solvents: converging on a unified picture. Acc Chem Res2017; 50: 1920–1927.
13.
LobodaOTunellIMinaevB, et al.Theoretical study of triplet state properties of free-base porphin. Chem Phys2005; 312: 299–309.
14.
MinaevBF. Quantum-chemical investigation of the mechanisms of the photosensitization, luminescence, and quenching of singlet1Δg oxygen in solutions. J. of Appl. Spectroscopy1985; 42: 518–523.
15.
ValievRRNasibullinRTCherepanovVN, et al.First-principles calculations of anharmonic and deuteration effects on the photophysical properties of polyacenes and porphyrinoids. Phys. Chem. Chem. Phys2020; 22: 22314–22323.
16.
AebisherDCzechSDynarowiczK, et al.Photodynamic therapy: past, current, and future. Int J Mol Sci2024; 25: 11325.
17.
DagarGGuptaAShankarA, et al.The future of cancer treatment: combining radiotherapy with immunotherapy. Front Mol Biosci2024; 11: 1409300.
18.
ZhangPHanTXiaH, et al.Advances in photodynamic therapy based on nanotechnology and its application in skin cancer. Front Oncol2022; 12: 836397.
19.
SakhnoTSakhnoYKuchmiyS. Clusteroluminescence in organic, inorganic, and hybrid systems: a review. Theor. Exp. Chem2022; 58: 297–327.
20.
SakhnoTSakhnoYKuchmiyS. Clusteroluminescence of unconjugated polymers: a review. Theor. Exp. Chem2023; 59: 75–106.
21.
WangXDingXYuB, et al.Tumor microenvironment-responsive polymer with chlorin e6 to interface hollow mesoporous silica nanoparticles-loaded oxygen supply factor for boosted photodynamic therapy. Nanotechnology2020; 31: 305709.
22.
SakhnoTIvashchenkoDSemenovA, et al.Clusteroluminogenic polymers: applications in biology and medicine (review article). Low Temp Phys2024; 50: 276–287.
23.
HongGChangJE. Enhancing cancer treatment through combined approaches: photodynamic therapy in concert with other modalities. Pharmaceutics2024; 16: 1420.
24.
AebisherDSzparaJBartusik-AebisherD. Advances in medicine: photodynamic therapy. Int J Mol Sci2024; 25: 8258.
25.
GrynyovBSakhnoTSenchishinV. Optically transparent and fluorescent polymers. Kharkiv, 2003, p. 1-575.
26.
ValievRHeYWeltzinT, et al.Wavelength-dependent intersystem crossing dynamics of phenolic carbonyls in wildfire emissions. Phys. Chem. Chem. Phys2025; 27: 998–1007.
27.
KorneevOSakhnoTKorotkovaI. Nanoparticles-based photosensitizers with effect of aggregation-induced emission. Biopolymers and Cell2019; 35: 249–267.
28.
BarashkovNSakhnoTNurmukhametovR, et al.Excimers of organic molecules. Russian Chem. Reviews1993; 62: 539–552.
29.
DiasLDMfouo-TyngaIS. Learning from nature: bioinspired chlorin-based photosensitizers immobilized on carbon materials for combined photodynamic and photothermal therapy. Biomimetics (Basel)2020; 5: 53.
30.
LimaEReisLV. Photodynamic therapy: from the basics to the current progress of N-heterocyclic-bearing dyes as effective photosensitizers. Molecules2023; 28: 5092.
31.
PlotnikovV. Regularities of the processes of radiationless conversion in polyatomic molecules. Intern. J. of Quantum Chem1979; 16: 527–541.
32.
NiJWangYZhangH, et al.Aggregation-Induced generation of reactive oxygen Species: mechanism and photosensitizer construction. Molecules2021; 26: 68.
33.
KwiatkowskiSKnapBPrzystupskiD, et al.Photodynamic therapy - mechanisms, photosensitizers and combinations. Biomed Pharmacother2018; 106: 1098–1107.
RobertsonCAEvansDHAbrahamseH. Photodynamic therapy (PDT): a short review on cellular mechanisms and cancer research applications for PDT. J Photochem Photobiol B2009; 96: –8.
36.
MushtaqAZhangHCuiM, et al.Corrigendum to “ROS-responsive chlorin e6 and silk fibroin loaded ultrathin magnetic hydroxyapatite nanorods for T1-magnetic resonance imaging guided photodynamic therapy in vitro” colloids surf. A: physicochem. Eng. Aspects 656 (part B). Colloids Surf, A2023; 665: 130513.
37.
KumarRDalalDGuptaK, et al.Photodynamic therapy and ROS. In: ChakrabortiS (ed.) Handbook of oxidative stress in cancer: therapeutic aspects. Singapore: Springer, 2022, pp.1325–1335.
38.
DąbrowskiJ. Chapter nine - reactive oxygen Species in photodynamic therapy: mechanisms of their generation and potentiation. Adv Inorg Chem2017; 70: 343–394.
39.
MinaevB. Spin-orbit coupling mechanism of singlet oxygen a1Δg quenching by solvent vibrations. Chem Phys2017; 483: 84–95.
40.
FonsecaSMPinaJArnautLG, et al.Triplet-state and singlet oxygen formation in fluorene-based alternating copolymers. J Phys Chem B2006; 110: 8278–8283.
41.
ErdenIKaradoğanBKılıçarslanFA, et al.New soluble 4-(4-formyl-2,6-dimethoxyphenoxy) substituted phthalocyanines: synthesis, characterization, photophysical and photochemical properties. Main Group Chem2022; 21: 421–430.
42.
CorreiaJHRodriguesJAPimentaS, et al.Photodynamic therapy review: principles, photosensitizers, applications, and future directions. Pharmaceutics2021; 13: 1332.
43.
KesselDOleinickNL. Photodynamic therapy and cell death pathways. Methods Mol Biol2010; 635: 35–46.
44.
DonohoeCSengeMOArnautLG, et al.Cell death in photodynamic therapy: from oxidative stress to anti-tumor immunity. Biochim Biophys Acta Rev Cancer2019; 1872: 188308.
45.
KutluÖDAvcilDErdoğmuşA. New water-soluble cationic indium (III) phthalocyanine bearing thioquinoline moiety; synthesis, photophysical and photochemical studies with high singlet oxygen yield. Main Group Chem2019; 18: 139–151.
46.
ÖncülGAÖztürkÖFPişkinM. Spectroscopic and photophysicochemical properties of zinc(II) phthalocyanine substituted with benzenesulfonamide units containing schiff base. Main Group Chem2022; 21: 997–1011.
47.
MarcusSMcIntyreW. Photodynamic therapy systems and applications. Expert Opin Emerg Drugs2002; 7: 321–334.
48.
FukuharaHYamamotoSKarashimaT, et al.Photodynamic diagnosis and therapy for urothelial carcinoma and prostate cancer: new imaging technology and therapy. Int J Clin Oncol2021; 26: 18–25.
49.
TaokaRMatsuokaYYamasakiM, et al.Photodynamic diagnosis-assisted transurethral resection using oral 5-aminolevulinic acid decreases residual cancer and improves recurrence-free survival in patients with non-muscle-invasive bladder cancer. Photodiagnosis Photodyn Ther2022; 38: 102838.
50.
WernerMLyuCStadlbauerB, et al.The role of shikonin in improving 5-aminolevulinic acid-based photodynamic therapy and chemotherapy on glioblastoma stem cells. Photodiagnosis Photodyn Ther2022; 39: 102987.
51.
AvendañoCMenéndezJ. Anticancer strategies involving radical species medicinal chemistry of anticancer drugs (third edition). Elsevier, 2023; 165–235. 10.1016/B978-0-12-818549-0.09991-X
52.
AzzouziARLebdaiSBenzaghouF, et al.Vascular-targeted photodynamic therapy with TOOKAD® soluble in localized prostate cancer: standardization of the procedure. World J Urol2015; 33: 937–944.
53.
KubrakTKarakułaMCzopM, et al.Advances in management of bladder cancer-the role of photodynamic therapy. Molecules2022; 27: 31.
54.
AzzouziABarretEMooreC, et al.TOOKAD((R)) soluble vascular-targeted photodynamic (VTP) therapy: determination of optimal treatment conditions and assessment of effects in patients with localised prostate cancer. BJU Int2013; 112: 766–774.
55.
LorenzKJMaierH. Squamous cell carcinoma of the head and neck. Photodynamic therapy with foscan] [article in German. HNO2008; 56: 402–409.
56.
KikuchiTAsakuraTAiharaH, et al.Photodynamic therapy of intestinal tumors with mono-L-aspartyl chlorin e6 (NPe6): a basic study. Anticancer Res2003; 23: 4897–4900.
57.
FanLJiangZXiongY, et al.Recent advances in the HPPH-based third-generation photodynamic agents in biomedical applications. Int J Mol Sci2023; 24: 17404.
58.
HuntDW. Rostaporfin (miravant medical technologies). IDrugs2002; 5: 180–186.
59.
MangTSAllisonRHewsonG, et al.A phase II/III clinical study of tin ethyl etiopurpurin (purlytin)-induced photodynamic therapy for the treatment of recurrent cutaneous metastatic breast cancer. Cancer J Sci Am1998; 4: 378–384.
60.
WongJJWLorenzSSelboPK. All-trans retinoic acid enhances the anti-tumour effects of fimaporfin-based photodynamic therapy. Biomed Pharmacother2022; 155: 113678.
61.
MooreCMEmbertonMBownSG. Photodynamic therapy for prostate cancer–an emerging approach for organ-confined disease. Lasers Surg Med2011; 43: 768–775.
62.
HsiRAKapatkinAStrandbergJ, et al.Photodynamic therapy in the canine prostate using motexafin lutetium. Clin Cancer Res2001; 7: 651–660.
63.
DuKLMickRBuschTM, et al.Preliminary results of interstitial motexafin lutetium-mediated PDT for prostate cancer. Lasers Surg Med2006; 38: 427–434.
64.
KellyJFSnellME. Hematoporphyrin derivative: a possible aid in the diagnosis and therapy of carcinoma of the bladder. J Urol1976; 115: 150–151.
65.
DattaSNLohCSMacRobertAJ, et al.Quantitative studies of the kinetics of 5-aminolaevulinic acid-induced fluorescence in bladder transitional cell carcinoma. Br J Cancer1998; 78: 1113–1118.
66.
van den BoogertJvan HillegersbergRde RooijFW, et al.5-Aminolaevulinic acid-induced protoporphyrin IX accumulation in tissues: pharmacokinetics after oral or intravenous administration. J Photochem Photobiol B1998; 44: 29–38.
67.
ZaakDFrimbergerDSteppH, et al.Quantification of 5-aminolevulinic acid induced fluorescence improves the specificity of bladder cancer detection. J Urol2001; 166: 1665–1669.
68.
UnyimeO. Photodynamic therapy. Urol Clin N Am1992; 19: 591–599.
69.
FabreMAFuseauEFicheuxH. Selection of dosing regimen with WST11 by monte carlo simulations, using PK data collected after single IV administration in healthy subjects and population PK modeling. J Pharm Sci2007; 96: 3444–3456.
70.
GrossSGileadAScherzA, et al.Monitoring photodynamic therapy of solid tumors online by BOLD-contrast MRI. Nat Med2003; 9: 1327–1331.
71.
Madar-BalakirskiNTempel-BramiCKalchenkoV, et al.Permanent occlusion of feeding arteries and draining veins in solid mouse tumors by vascular targeted photodynamic therapy (VTP) with tookad. PLoS One2010; 5: e10282.
72.
NoweskiARoosenALebdaiS, et al.Medium-term follow-up of vascular-targeted photodynamic therapy of localized prostate cancer using TOOKAD soluble WST-11 (phase II trials). Eur Urol Focus2019; 5: 1022–1028.
73.
GheewalaTSkworTMunirathinamG. Photosensitizers in prostate cancer therapy. Oncotarget2017; 8: 30524–30538.
74.
ChenQHuangZLuckD, et al.Preclinical studies in normal canine prostate of a novel palladium-bacteriopheophorbide (WST09) photosensitizer for photodynamic therapy of prostate cancers. Photochem Photobiol2002; 76: 438–445.
75.
HuangZChenQDoleKC, et al.The effect of tookad-mediated photodynamic ablation of the prostate gland on adjacent tissues—in vivo study in a canine model. Photochem Photobiol Sci2007; 6: 1318–1324.
76.
HuangZChenQTrncicN, et al.Effects of Pd-bacteriopheophorbide (TOOKAD)-mediated photodynamic therapy on canine prostate pretreated with ionizing radiation. Radiat Res2004; 161: 723–731.
77.
DoleKCChenQHetzelFW, et al.Effects of photodynamic therapy on peripheral nerve: in situ compound-action potentials study in a canine model. Photomed Laser Surg2005; 23: 172–176.
78.
PinhoSCoelhoJMPGasparMM, et al.Advances in localized prostate cancer: a special focus on photothermal therapy. Eur J Pharmacol2024; 983: 176982.
79.
TraceyATNogueiraLMAlvimRG, et al.Focal therapy for primary and salvage prostate cancer treatment: a narrative review. Transl Androl Urol2021; 10: 3144–3154.
80.
SjobergHTPhilippouYMagnussenAL, et al.Tumor irradiation combined with vascular-targeted photodynamic therapy enhances antitumor effects in pre-clinical prostate cancer. Br J Cancer2021; 125: 534–546.
81.
YipWSjobergDNogueiraL, et al.Final results of a phase i trial of wst11 (tookad soluble) vascular-targeted photodynamic therapy for upper tract urothelial carcinoma. J Urol2022; 207: e1013.
82.
TsuberVKadamovYBrautigamL, et al.Mutations in cancer cause gain of cysteine, histidine, and tryptophan at the expense of a net loss of arginine on the proteome level. Biomolecules2017; 7: 49.
83.
MooreCMPendseDEmbertonM. Photodynamic therapy for prostate cancer — a review of current status and future promise. Nature Clin Practice Urology2009; 6: 18–30.
84.
SlesarevskayaMNSokolovAVKuzminIV. Photosensitizer in diagnosis and treatment of oncological diseases. Urology Reports (St.-Petersburg)2013; 3: 10–13.
85.
ZaakDStrokaRHoppnerM, et al.Photodynamic therapy by means of 5-ALA induced PP1X in human prostate cancer-preliminary results. Med Laser Appl2003; 18: 91–95.
86.
TrachtenbergJWeersinkRADavidsonSR, et al.Vascular-targeted photodynamic therapy (padoporfin, WST09) for recurrent prostate cancer after failure of external beam radiotherapy: a study of escalating light doses. BJU Int2008; 102: 556–562.
87.
TrachtenbergJBogaardsAWeersinkRA, et al.Vascular targeted photodynamic therapy with palladium-bacteriopheophorbide photosensitizer for recurrent prostate cancer following definitive radiation therapy: assessment of safety and treatment response. J Urol2007; 178: 1974–1979.
88.
ChoH-JParkS-JJungWH, et al.Injectable single-component peptide depot: autonomously rechargeable tumor photosensitization for repeated photodynamic therapy. ACS Nano2020; 14: 15793–15805.
89.
Al SaffarHChenDCDelgadoC, et al.The current landscape of prostate-specific membrane antigen (PSMA) imaging biomarkers for aggressive prostate cancer. Cancers (Basel)2024; 16: 39.
90.
WangXSunRWangJ, et al.A low molecular weight multifunctional theranostic molecule for the treatment of prostate cancer. Theranostics2022; 12: 2335–2350.
91.
ShirkeAAWalkerEChavaliS, et al.A synergistic strategy combining chemotherapy and photodynamic therapy to eradicate prostate cancer. Int J Mol Sci2024; 25: 7086.
