Advances in photosensitizer-related design for photodynamic therapy

Abstract

Photodynamic therapy (PDT) is highly effective in treating tumors located near body surface, offering strong tumor suppression and low damage to normal tissue nearby. PDT is also effective for treating a number of other conditions. PDT not only provide a precise and selective method for the treatment of various diseases by itself, it can also be used in combination with other traditional therapies. Because PDT uses light as the unique targeting mechanism, it has simpler and more direct targeting capability than traditional therapies. The core material of a PDT system is the photosensitizer which converts light energy to therapeutic factors/substances. Different photosensitizers have their distinct characteristics, leading to different advantages and disadvantages. These could be enhanced or compensated by using proper PDT system. Therefore, the selected type of photosensitizer would heavily influence the overall design of a PDT system. In this article, we evaluated major types of inorganic and organic PDT photosensitizers, and discussed future research directions in the field.

Keywords: Combination therapy; Photodynamic therapy; Photosensitizer; Porphyrin; Tumour treatment.

Graphical abstract

Fig. 1.

(A, B) Diagram of electron energy level change under NIR radiation. (C) O₂ generation curve, (D) ESR spectra O₂•⁻(DMSO), (E) OH•(water). Reproduced with permission from . Copyrights 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fig. 2.

Schematic diagram of light induced nanoparticles larger than nuclear pore into nucleus. Reproduced with permission from[22]. Copyrights 2019 Elsevier Ltd.

Fig. 3.

The main geometric parameters and chemical composition of the system studied. Reproduced with permission from[23]. Copyrights 2020 Wiley Periodicals, Inc.

Fig. 4.

Schematic diagram of PDT combined with chemotherapy with photoactivation. Reproduced with permission from . Copyrights 2021 Bentham Science Publishers.

Fig. 5.

Schematic diagram of PDT photosensitizer system of Mn compound with photodynamic agent and pH response. Reproduced with permission from . Copyrights 2021 Informa UK Limited.

Fig. 6.

Characterization and preparation of four arm PEG-COOH. The structure diagram and principle of AGCN—NS modified by four arm PEG-COOH. AGCN—NS covalently binds to PEG via amide bond (blue). Reproduced with permission from . Copyrights 2020 Elsevier Inc.

Fig. 7.

Schematic diagram of the formation of O₂ and further formation of ¹O₂ catalyzed by MnO₂ in HA/ICG-CuS@hMnO₂ under near-infrared light of 808 nm. Reproduced with permission from . Copyrights 2020 Elsevier B.V.

Fig. 8.

Schematic of Irpy-HA for PDT in this study. Reproduced with permission from[31]. Copyrights 2019 Elsevier Ltd.

Fig. 9.

Schematic of the preparation for Zn²⁺,K⁺-C₃N₄ nanosheets. Reproduced with permission from . Copyrights 2020 Elsevier B.V.

Fig. 10.

Preparation and application of LSPR and GNBP-BPNS nanocomposites reinforced PTT-PDT. Reproduced with permission from . Copyrights 2020 Acta Materialia Inc, Published by Elsevier Ltd.

Fig. 11.

Schematic of autoamplification PDT in NIR and mechanism of ¹O₂ stimulation of cleavage. Reproduced with permission from . Copyrights 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Fig. 12.

The flowchart of synthetic of chlorin I and chlorinⅡ, a, b, c, d, e, f are available in references. Reproduced with permission from . Copyrights 2020 Elsevier Masson SAS.

Fig. 13.

(A, B) Evaluation of in vitro effects for NP-sfb/ce6 in PDT. (C) K1-Tumor growth curve after the first treatment. (D) The weights of K1-tumors after the treatment. Reproduced with permission from . Copyrights 2020 Elsevier Ltd.

Fig. 14.

(A) Elative spectral distribution of the plate-type LEDs (a) and flexible-type LEDs (b). (B) ROS produce by PpIX under different light sources. Reproduced with permission from . Copyrights 2019 Japanese Society for Investigative Dermatology, Published by Elsevier B.V.

Fig. 15.

(A) Decompose H₂O₂ to O₂ in a temperature responsive manner, and increase the O₂ in tumor site, then the tumors were killed by PDT. (B) Evaluation of in vitro effects for PB@PMO-5-ALA in PDT. Reproduced with permission from . Copyrights 2020 Elsevier Inc.

Fig. 16.

TGF-β1 analyzed by ELISA after PDT in this study. Reproduced with permission from . Copyrights 2020 Published by Elsevier B.V.

Fig. 17.

(A) Schematic of the structure for PMO skeleton, the reaction pathway of benzene hydroxylation and protoporphyrin IX (PpIX) loading, and the mechanism of photoinduced biological effects. (B) Evaluation of in vitro effects for PMO-PpIX in MTT. Reproduced with permission from . Copyrights 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Fig. 18.

Schematic for preparation of PEG-CHO-Apt-PA, and the acid response principle in TME (pH=6.5). Reproduced with permission from . Copyrights 2020 Published by Elsevier Ltd.

Fig. 19.

Tumor inhibition in vivo. (A, B) Temperature change of tumor site after receiving light. (C, D) Tumor volume and tumor morphology after treatment in different group. Reproduced with permission from . Copyrights 2019 Elsevier Ltd.

Fig. 20.

Semiquantitative data of ROS production in vivo for different materials after intravenous illumination. Reproduced with permission from . Copyrights 2020 Elsevier Ltd.

Fig. 21.

(A) the structure of the nano-drug delivery system. (B,C,D,E,G) In vivo efficacy of TAT+AzoNPs@ (Ce6+TPZ). (I) control group, (II) the system without light, (III) Free (Ce6+TPZ) with light, (IV) TAT+AzoNPs@ TPZ with light, (V) TAT+AzoNPs@ Ce6 with light, (VI) NNPs@(Ce6+TPZ) with light, (VII) AzoNPs@(Ce6+TPZ) with light, and (VIII) the system with light. Reproduced with permission from . Copyrights 2020 Elsevier Ltd.

Fig. 22.

(A) Synthesis route of new tribenzo porphyrin, the synthesis steps are shown in the original text. (B) The number of viable S.aureus after PDT using TBP. Reproduced with permission from . Copyrights 2020 Elsevier B.V.

Fig. 23.

Parasite load of mice infected with Amazon L. amazonensis treated with TiO₂/Zn in PDT. Reproduced with permission from . Copyrights 2020 Elsevier B.V.

Fig. 24.

Analysis of viable bacteria count after PDT treatment. Reproduced with permission from . Copyrights 2020 Elsevier B.V.