A high therapeutic efficacy of polymeric prodrug nano-assembly for a combination of photodynamic therapy and chemotherapy

Xiaoqing Yi,Jun Dai,Fan Xia,Min Xu,Shijie Zhen,Xiaoding Lou,Yingyan Han,Xiaojin Zhang,Zujin Zhao

doi:10.1038/s42003-018-0204-6

Abstract

Combination of photodynamic therapy and chemotherapy has been emerging as a new strategy for cancer treatment. Conventional photosensitizer tends to aggregate in aqueous media, which causes fluorescence quenching, reduces reactive oxygen species (ROS) production, and limits its clinical application to photodynamic therapy. Traditional nanoparticle drug delivery system for chemotherapy also has its disadvantages, such as low drug loading content, drug leakage, and off-target toxicity for normal tissues. Here, we developed a reduction-sensitive co-delivery micelles TB@PMP for combinational therapy, which composed of entrapping a red aggregation-induced emission fluorogen (AIEgen) for photodynamic therapy and PMP that contains a reduction-sensitive paclitaxel polymeric prodrug for chemotherapy. AIEgen photosensitizer illustrates a much improved photostability and ROS production efficiency in aggregate state and PMP loads a high dose of paclitaxel and carries a smart stimuli-triggered drug release property. This co-delivery system provides a better option that replaces AIEgen photosensitizer for cancer diagnosis and therapy.

Highlights

Combination of photodynamic therapy and chemotherapy has been emerging as a new strategy for cancer treatment
The polymeric prodrug PMP was synthesized according to our previous report[45], and the partial characterization is shown in Supplementary Figures 1 and 2
PM and PMP polymeric micelles were prepared by dialysis method, and the critical micelles concentrations (CMC) of PM and PMP were 13.7 and 7.9 mg L−1, respectively, determined by fluorescence measurement using pyrene as a probe (Table 1)

Summary

Introduction

Combination of photodynamic therapy and chemotherapy has been emerging as a new strategy for cancer treatment. After incubated with TB@PMP micelles for 4 h and irradiated with white light (100 mW cm−2) for 3 min, HeLa cells were investigated using CLSM.

Results

Conclusion