Heavy atom-free semiconducting polymer with high singlet oxygen quantum yield for prostate cancer synergistic phototherapy

Abstract

Photodynamic and photothermal synergistic therapy are newly developed approaches for cancer treatment. The design and preparation of photosensitizers of high phototoxicity as well as low dark toxicity are of increasing significance in minimizing the side effects and maximizing the phototherapy efficacy of such treatments. In this study, a heavy atom-free copolymer NDNT was designed and synthesized by the Stille coupling reaction. This compound shows a high singlet oxygen quantum yield of 55.2%, guaranteeing an excellent phototherapy efficacy. The nanoparticles (NPs) of NDNT obtained by nanoprecipitation with DSPE-PEG_-2000 with an average diameter of 65 nm exhibit considerably high phototoxicity towards human prostate cancer cells (Du145) because their half inhibitory concentration (IC₅₀) is as low as 3.8 μg mL⁻¹. Simultaneously, the dark toxicity of the NPs is almost negligible, even at a high concentration. Furthermore, an in vivo study with laser irradiation by photodynamic and photothermal synergistic therapy demonstrates that the NPs are capable of inhibiting a Du145 tumor growth, compared with the control and dark group, suggesting the low dark toxicity and high phototoxicity of such NPs. The H&E stained pictures of the normal tissues show that no obvious damage occurred, indicating the biosafety of the NDNT NPs. These results provide a strategy for designing heavy atom-free copolymers for phototherapy both in vitro and in vivo.