In Situ Catalytic Reaction for Solving the Aggregation of Hydrophobic Photosensitizers in Tumor

Abstract

The aggregation of hydrophobic photosensitizers limits the therapeutic effect of photodynamic therapy (PDT). Improving the hydrophilicity of photosensitizers can reduce their aggregation for enhancing PDT. Herein, a nanosystem (TPFcNP) is developed by a hydrophobic photosensitizer 5,10,15,20-tetrakis(4-methacryloyloxyphenyl)porphyrin (TMPP) containing multiple carbon−carbon double bonds and a ferrocenecontaining amphiphilic block copolymer (PEG-b-PMAEFc), which catalyzes hydrogen peroxide (H 2 O 2 ) to produce hydroxyl radicals ( • OH) in a tumor microenvironment by the Fenton reaction. The • OH could catalyze the addition reaction between the carbon− carbon double bonds of TMPP and overexpressed water-soluble glutathione (GSH) in tumor cells, which greatly improves the hydrophilicity of photosensitizers and reduces their aggregation. Experiments in vitro and in vivo have proved that this strategy significantly enhances the therapeutic efficacy of PDT. Catalyzing intracellular reactions in situ by making use of the tumor microenvironment will open up a new opportunity to solve the aggregation of materials in the tumor for cancer treatment.

Photodynamic therapy regulates fate of cancer stem cells through reactive oxygen species

“…In fact, the Fenton reaction is very commonly used in the design and synthesis of nano-photosensitizers. Currently, some studies have used the Fenton reaction to increase the concentration of O 2 [ 174 ] or hydroxyl radicals[ 175 ] in the tumor microenvironment, and others used it to directly kill CSCs. PDT combined with the Fenton reaction[ 176 ] is a feasible treatment method for CSCs showing strong drug resistance.…”

Cutting‐edge advancements of nanomaterials for medi‐translatable noninvasive theranostic modalities

“…17 Photodynamic therapy (PDT) Ref. [31][32][33][34][35][36][37][38][39] Magneto-acoustic imaging (MAI) Ref. 18 PTT-PDT Ref.…”

“…(Reproduced from Bu et al, In situ catalytic reaction for solving the aggregation of hydrophobic photosensitizers in tumor, ACS Appl Mater Interfaces, 2020, 12, 5624 with the permission of American Chemical Society. 39 ) nanosystem using a hydrophobic photosensitizer 5,10,15,20-tetrakis(4-methacryloyloxyphenyl)porphyrin (TMPP) with carbon double bonds and a ferrocenecontaining amphiphilic block copolymer (PEG-b-PMAEFc) was constructed (Figure 10). 39 The production of singlet oxygen has been greatly enhanced with pH ranges from 6.5 to 7.2 (the environment of normal cells to tumor cells), and the in situ catalytic reaction of tumor cells provided a new opportunity for the development of hydrophobic photosensitizers for PDT.…”

Recent advances in theranostic agents based on natural products for photodynamic and sonodynamic therapy

“…Wang et al constructed a nanosystem (TPFcNP) by assembling a hydrophobic theranostic agent containing multiple alkenyls in the terminal of tetrakis(4-methacryloyloxyphenyl)porphyrin (TMPP) and an amphiphilic copolymer with ferrocene unit (PEG-b-PMAEFc) to overcome the hydrophobicity of porphyrin. 38 Figure 3 shows that the ferrocene unit in TPFcNP can catalyze H 2 O 2 overexpressed in the acidic tumor microenvironment through a Fenton reaction to generate hydroxyl radicals. The produced hydroxyl radicals further promote the addition reaction of the alkenyl terminal of the hydrophobic TMPP with overexpressed glutathione (GSH), resulting in a TMPP-GSH adduct with enhanced hydrophilicity.…”

“…Reprinted with permission. 38 Copyright 2020, American Chemical Society hydroxyl and superoxide radicals. Although the active oxygen yield of the chemically modified hypocrellin is slightly decreased, it is still sufficient for PDT in hypoxic tumors.…”