Reduction-Induced Decomposition and Self-Aggregation Strategy To Induce Reactive Oxygen Species Generation for Cancer Therapy.

Conventional photodynamic therapy used for cancer treatment is incapable of achieving satisfactory therapeutic effects because of a low encapsulation efficiency and uncontrolled photosensitizer leakage. Herein, we introduce a novel nanoparticle system with reduction-induced decomposition and photosensitizer self-aggregation capability to upregulate reactive oxygen species (ROS) level under UV irradiation in cancer cells, leading to cancer cells apoptosis. The nanoparticles could be self-assembled with low critical micellar concentration using amphiphilic polymers composed of polyethylene glycol segment and a bis(pyrene) molecule with a disulfide bond as a reduction linker. The 1 HNMR and transmission electron microscopy results showed that the responsive disulfide bonds in the nanoparticles were specifically cleaved in the reductive environment, which resulted in in situ self-aggregation of the pyrene residues, which was confirmed by the results of UV and fluorescence spectra. Furthermore, confocal laser microscopy and flow cytometry demonstrated that the ROS level was upregulated in cancer cells exposed to nanoparticles under UV irradiation compared to insensitive group, causing cells apoptosis. Therefore, this strategy opens a new method for cancer therapy.