A Self‐Degradable Conjugated Polymer for Photodynamic Therapy with Reliable Postoperative Safety

Abstract

As a noninvasive therapeutic technique, photodynamic therapy (PDT) has attracted numerous research interests for cancer therapy. Nevertheless, the residual photosensitizers (PSs) still produce reactive oxygen species (ROS) and damage normal cells under sunlight after PDT, which limits their practical application in clinic. Herein, the authors propose a self-degradable type-I PS based on conjugated polymer, which is composed of aggregation-induced emission (AIE) and imidazole units. Due to the effective conjugated skeleton and unique AIE properties, thus-obtained polymers can effectively generate superoxide radical (O 2 −• ) through the type-I process under light irradiation, which is ideal for hypoxic tumors treatment. Intriguingly, under light irradiation, O 2 −• produced by the conjugated polymers can further lead to the self-degradation of the polymer to form nontoxic micro-molecules. It not only helps to resolve the potential phototoxicity problems of residual PSs, but also can accelerate the metabolism of the conjugated polymers to avoid the potential biotoxicity of drug accumulation. This work develops a self-degradable type-I PS, which can turn off the generation of ROS in time after PDT, providing a novel strategy to balance the PDT effect and postoperative safety.

A chemical biology toolbox to overcome the hypoxic tumor microenvironment for photodynamic therapy: a review

“…Based on the residual problem of photosensitizers in the body after photodynamic therapy, Huang et al designed and synthesized an AIE photosensitizer that can achieve self-degradation after treatment. 23,24 In this work, self-degradable conjugated CP1 was obtained by alternately assembling AIE molecules with imidazoles (Fig. 3a).…”

Design and structural regulation of AIE photosensitizers for imaging-guided photodynamic anti-tumor application

“…4,5 Subsequently, the excited triplet state of PSs sensitizes the surrounding oxygen to produce cytotoxic reactive oxygen species (ROS) containing singlet oxygen ( 1 O 2 ), hydroxy radical ( • OH), superoxide radical ( • O 2 − ), etc. 6,7 The PDT process could affect the intracellular metabolism, damage the cell structure and inactivate cellular proteins, thereby killing malignant tumor cells which interact with PSs. [8][9][10] This method also efficiently alleviates the issue of development of drug resistance.…”

Rational Modulation of BODIPY Photosensitizers to Design Metal–Organic Framework-Based NIR Nanocomposites for High-Efficiency Photodynamic Therapy in a Hypoxic Environment

“…However, due to the immortal proliferation of tumor cells, the capillaries of the tumor tissue are distorted, resulting in severe hypoxia in the tumor microenvironment. − Additionally, PDT treatment can lead to severe damage to the tumor site, including the collapse of microvessels, which further affects the supply of O 2 . The hypoxic environment caused by the above reasons will lead to a poor PDT effect. − …”