Modern outlook for the use of photosensitizers with aggregation-induced emission in treatment of malignant tumors

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

Photodynamic therapy (PDT) is actively developing, becoming one of the important methods of non-invasive treatment of various oncological and infectious diseases. It is usually carried out using three main components: a photosensitizer, light, and oxygen. The key factors for the effective use of PDT are reactogenic oxygen species, which are produced during the oxidation of photosensitizers under the influence of light irradiation.

To increase the production of reactogenic oxygen species, a technique was proposed for creating photosensitizers with aggregation-induced emission. At the present stage in oncology, the following PDT methods using photosensitizers with aggregation-induced emission are distinguished: PDT, absorbing near infrared radiation; enzyme- or glutathione-activated PDT; hypoxic PDT, and synergistic therapy.

Compared to visible light, near infrared radiation (700–1700 nm) has been shown to be more effective and safer due to reduced photodamage, less scattering, and deeper light penetration. The development of activated photosensitizers is an effective way to overcome the uncontrolled phototoxicity of photosensitizers during long-term PDT in vivo, providing controlled death of tumor cells. The oxygen concentration in tumor tissue varies depending on tumor progression, angiogenesis, metabolism, and metastasis. Therefore, the development of photosensitizers capable of effectively fluorescing under hypoxic conditions, including catalyzing intracellular substrates with the formation of oxygen and stimulating the production of reactogenic oxygen species through the type I mechanism, has become a potential solution to the problem of PDT of solid tumors.

The therapeutic efficacy of a single PDT method, as well as most treatment methods in modern oncology, is limited. Therefore, a significant direction is the development of multifunctional treatment systems for synergistic therapy of tumors. Synergistic chemotherapy and PDT is an important area of treatment in oncology. The combination of PDT and immunotherapy is also a promising direction in the treatment of malignant neoplasms.

There are obvious prospects for PDT in oncology not as a separate method of treatment, but as part of a complex multimodal treatment, including chemotherapy, radiation therapy, surgical treatment, and immunotherapy.

About the authors

Alexander E. Tseimakh

Altai State Medical University

Author for correspondence.
Email: alevtsei@rambler.ru
ORCID iD: 0000-0002-1199-3699
SPIN-code: 5795-0530

MD, Cand. Sci. (Med.), Associate Professor

Russian Federation, Barnaul

Alexander F. Lazarev

Altai State Medical University

Email: lazarev@akzs.ru
ORCID iD: 0000-0003-1080-5294
SPIN-code: 1161-8387

MD, Dr. Sc. (Med.), Professor

Russian Federation, Barnaul

Yakov N. Shoykhet

Altai State Medical University

Email: starok100@mail.ru
ORCID iD: 0000-0002-5253-4325
SPIN-code: 6379-3517

MD, Dr. Sc. (Med.), Professor, Corresponding Member of the Russian Academy of Sciences

Russian Federation, Barnaul

References

  1. Li X, Lee D, Huang JD, Yoon J. Phthalocyanine-assembled nanodots as photosensitizers for highly efficient type I photoreactions in photodynamic therapy. Angew Chem Int Ed Engl. 2018;57(31):9885–9890. doi: 10.1002/anie.201806551
  2. Tappenier HV. Therapeuthe versuche mit fluoreszierenden stiffen. Muench Med Wochenschr. 1903;47:2042–2044.
  3. Sun Y, Zhao D, Wang G, et al. Recent progress of hypoxia-modulated multifunctional nanomedicines to enhance photodynamic therapy: opportunities, challenges, and future development. Acta Pharm Sin B. 2020;10(8):1382–1396. doi: 10.1016/j.apsb.2020.01.004
  4. Chilakamarthi U, Giribabu L. Photodynamic therapy: past, present and future. Chem Rec. 2017;17(8):775–802. doi: 10.1002/tcr.201600121
  5. Bonnett R. Photosensitizers of the porphyrin and phthalocyanine series for photodynamic therapy. Chem Soc Rev. 1995;(1):19–33.
  6. Sun J, Hu F, Ma Y, et al. AIE-based systems for imaging and image-guided killing of pathogens in handbook of aggregation-induced emission. Vol. 3. In: Tang Y, Tang BZ, editors. Handbook of aggregation-induced emission. Hoboken: John Wiley & Sons Ltd; 2022. P. 297–327. doi: 10.1002/9781119643098.ch52
  7. Sobotta L, Skupin-Mrugalska P, Piskorz J, Mielcarek J. Porphyrinoid photosensitizers mediated photodynamic inactivation against bacteria. Eur J Med Chem. 2019;175:72–106. doi: 10.1016/j.ejmech.2019.04.057
  8. Oyim J, Omolo CA, Amuhaya EK. Photodynamic antimicrobial chemotherapy: advancements in porphyrin-based photosensitize development. Front Chem. 2021;9:635344. doi: 10.3389/fchem.2021.635344
  9. Martínez-Cayuela M. Oxygen free radicals and human disease. Biochimie. 1995;77(3):147–161. doi: 10.1016/0300-9084(96)88119-3
  10. Plaetzer K, Kiesslich T, Verwanger T, Krammer B. The modes of cell death induced by PDT: an overview. Med Laser App. 2003;18(1):7–19. doi: 10.1078/1615-1615-00082
  11. Mroz P, Yaroslavsky A, Kharkwal GB, Hamblin MR. Cell death pathways in photodynamic therapy of cancer. Cancers (Basel). 2011;3(2):2516–2539. doi: 10.3390/cancers3022516
  12. Wang G, Gu X, Tang BZ. Chapter 17 AIEgen-based photosensitizers for photodynamic therapy. Vol. 2. In: Gu X, Tang BZ, edtors. Aggregation-induced emission applications in biosensing, bioimaging and biomedicine. Berlin; 2022. P. 485–522.
  13. Kasha M. Energy transfer mechanisms and the molecular excition model for molecular aggregates. Radiat Res. 1963;20:55–70.
  14. Yang L, Wang X, Zhang G, et al. Aggregation-induced intersystem cROSsing: a novel strategy for efficient molecular phosphorescence. Nanoscale. 2016;8(40):17422–17426. doi: 10.1039/c6nr03656b
  15. Ji C, Gao Q, Dong X, et al. Size-reducible nanodrug with an aggregation-enhanced photodynamic effect for deep chemo-photodynamic therapy. Angew Chem Int Ed Engl. 2018;57(35):11384–11388. doi: 10.1002/anie.201807602
  16. Lee E, Li X, Oh J, et al. A boronic acid-functionalized phthalocyanine with an aggregation-enhanced photodynamic effect for combating antibiotic-resistant bacteria. Chem Sci. 2020;11(22):5735–5739. doi: 10.1039/d0sc01351j
  17. Hsieh MC, Chien CH, Chang CC, Chang TC. Aggregation induced photodynamic therapy enhancement based on linear and nonlinear excited FRET of fluorescent organic nanoparticles. J Mater Chem B. 2013;1(18):2350–2357. doi: 10.1039/c3tb00345k
  18. Uchoa AF, de Oliveira KT, Baptista MS, et al. Chlorin photosensitizers sterically designed to prevent self-aggregation. J Org Chem. 2011;76(21):8824–8832. doi: 10.1021/jo201568n
  19. Tada DB, Baptista MS. Photosensitizing nanoparticles and the modulation of ROS generation. Front Chem. 2015;3:33. doi: 10.3389/fchem.2015.00033
  20. Luo J, Xie Z, Lam JW, et al. Aggregation-induced emission of 1-methyl-1,2,3,4,5-pentaphenylsilole. Chem Commun (Camb). 2001;(18):1740–1741. doi: 10.1039/b105159h
  21. Hong Y, Lam JW, Tang BZ. Aggregation-induced emission. Chem Soc Rev. 2011;40(11):5361–5388. doi: 10.1039/c1cs15113d
  22. Mei J, Hong Y, Lam JW, et al. Aggregation-induced emission: the whole is more brilliant than the parts. Adv Mater. 2014;26(31):5429–5479. doi: 10.1002/adma.201401356
  23. Mei J, Leung NL, Kwok RT, et al. Aggregation-induced emission: together we shine, united we soar! Chem Rev. 2015;115(21):11718–11940. doi: 10.1021/acs.chemrev.5b00263
  24. Zha M, Yang G, Li Y, et al. Recent advances in aiegen-based photodynamic therapy and immunotherapy. Adv Healthc Mater. 2021;10(24):2101066. doi: 10.1002/adhm.202101066
  25. Wang S, Wang X, Yu L, Sun M. Progress and trends of photodynamic therapy: from traditional photosensitizers to AIE-based photosensitizers. Photodiagn Photodyn Ther. 2021;34:102254. doi: 10.1016/j.pdpdt.2021.102254
  26. Wang L, Hu R, Qin A, Tang BZ. Conjugated polymers with aggregation-induced emission characteristics for fluorescence imaging and photodynamic therapy. ChemMedChem. 2021;16(15):2330–2338. doi: 10.1002/cmdc.202100138
  27. Liu S, Feng G, Tang BZ, Liu B. Recent advances of AIE light-up probes for photodynamic therapy. Chem Sci. 2021;12(19):6488–6506. doi: 10.1039/d1sc00045d
  28. He Z, Tian S, Gao Y, et al. Luminescent AIE dots for anticancer photodynamic therapy. Front Chem. 2021;9:672917. doi: 10.3389/fchem.2021.672917
  29. Chen H, Wan Y, Cui X, et al. Recent advances in hypoxia-overcoming strategy of aggregation-induced emission photosensitizers for efficient photodynamic therapy. Adv Healthc Mater. 2021;10(24):210607. doi: 10.1002/adhm.202101607
  30. Dai J, Wu X, Ding S, et al. Aggregation-induced emission photosensitizers: from molecular design to photodynamic therapy. J Med Chem. 2020;63(5):1996–2012. doi: 10.1021/acs.jmedchem.9b02014
  31. Zhang R, Duan Y, Liu B. Recent advances of AIE dots in NIR imaging and phototherapy. Nanoscale. 2019;11(41):19241–19250. doi: 10.1039/c9nr06012j
  32. Hu F, Xu S, Liu B. Photosensitizers with aggregation-induced emission: materials and biomedical applications. Adv Mater. 2018;30(45):1801350. doi: 10.1002/adma.201801350
  33. Tu Y, Zhao Z, Lam JWY, Tang BZ. Aggregate science: much to explore in the meso world. Matter. 2021;(4):338–349.
  34. Gu B, Wu W, Xu G, et al. Precise two-photon photodynamic therapy using an efficient photosensitizer with aggregation-induced emission characteristics. Adv Mater. 2017;29(28). doi: 10.1002/adma.201701076
  35. Li Y, Tang R, Liu X, et al. Bright aggregation-induced emission nanoparticles for two-photon imaging and localized compound therapy of cancers. ACS Nano. 2020;14(12):16840–16853. doi: 10.1021/acsnano.0c05610
  36. Lovell JF, Liu TW, Chen J, Zheng G. Activatable photosensitizers for imaging and therapy. Chem Rev. 2010;110(5):2839–2857. doi: 10.1021/cr900236h
  37. Xiong Y, Xiao C, Li Z, Yang X. Engineering nanomedicine for glutathione depletion-augmented cancer therapy. Chem Soc Rev. 2021;50(10):6013–6041. doi: 10.1039/d0cs00718h
  38. Yang N, Xiao W, Song X, et al. Recent advances in tumor microenvironment hydrogen peroxide-responsive materials for cancer photodynamic therapy. Nano-Micro Lett. 2020;12(1):15. doi: 10.1007/s40820-019-0347-0
  39. Wang Y, Shi L, Wu W, et al. Tumor-activated photosensitization and size transformation of nanodrugs. Adv Funct Mater. 2021;31(16):2010241. doi: 10.1002/adfm.202010241
  40. Ji S, Gao H, Mu W, et al. Enzyme-instructed self-assembly leads to the activation of optical properties for selective fluorescence detection and photodynamic ablation of cancer cells. J Mater Chem B. 2018;6(17):2566–2573. doi: 10.1039/c7tb02685d
  41. Zhao X, Dai Y, Ma F, et al. Molecular engineering to accelerate cancer cell discrimination and boost AIE-active type I photosensitizer for photodynamic therapy under hypoxia. Chem Eng J. 2021;410:128133. doi: 10.1016/j.cej.2020.128133
  42. Shi L, Hu F, Duan Y, et al. Hybrid nanospheres to overcome hypoxia and intrinsic oxidative resistance for enhanced photodynamic therapy. ACS Nano. 2020;14(2):2183–2190. doi: 10.1021/acsnano.9b09032
  43. Yi X, Dai J, Han Y, et al. A high therapeutic efficacy of polymeric prodrug nano-assembly for a combination of photodynamic therapy and chemotherapy. Commun Biol. 2018;1:202. doi: 10.1038/s42003-018-0204-6
  44. Wang G, Zhou L, Zhang P, et al. Fluorescence self-reporting precipitation polymerization based on aggregation-induced emission for constructing optical nanoagents. Angew Chem Int Ed Engl. 2020;59(25):10122–10128. doi: 10.1002/anie.201913847
  45. Galluzzi L, Buqué A, Kepp O, et al. Immunogenic cell death in cancer and infectious disease. Nat Rev Immunol. 2017;17(2):97–111. doi: 10.1038/nri.2016.107
  46. Yang W, Zhang F, Deng H, et al. Smart nanovesicle-mediated immunogenic cell death through tumor microenvironment modulation for effective photodynamic immunotherapy. ACS Nano. 2020;14(1):620–631. doi: 10.1021/acsnano.9b07212
  47. Chen C, Ni X, Jia S, et al. Massively evoking immunogenic cell death by focused mitochondrial oxidative stress using an AIE luminogen with a twisted molecular structure. Adv Mater. 2019;31(52):e1904914. doi: 10.1002/adma.201904914
  48. Li J, Ou H, Ding D. Recent progress in boosted PDT induced immunogenic cell death for tumor immunotherapy. Chem Res Chin Univ. 2021;37:83–89. doi: 10.1007/s40242-021-0402-5

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. Photochemical reactions of types I and II in photodynamic therapy (Yablonsky diagram) [12].

Download (207KB)
Indexing metadata

Copyright (c) 2022 Eco-Vector

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
 


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies