Random Ternary Copolymers with Adjustable Monomer Ratios Facilitate Efficient Near-Infrared II Imaging-Guided Phototherapy

The use of near-infrared (NIR) laser-excited phototheranostic agents has shown promise in enhancing phototherapy and facilitating NIR fluorescence imaging for deep-seated tumors. However, many NIR phototheranostic agents exhibit weak efficacy in second near-infrared (NIR-II) imaging-guided single-mode photothermal therapy. To address this limitation, a series of ternary copolymers containing triphenylamine, carbazole, and benzobisthiadiazole have been specifically designed and synthesized. The main focus is to assess how different proportions of structural units along the conjugated backbone, along with various triphenylamine derivatives, affect the photophysical properties of these copolymers. Additionally, their ability to generate reactive oxygen species (ROS) and their photothermal performance under NIR laser irradiation are examined with emphasis. Among these copolymers, PTCBT-CN253 stands out for its exceptional performance, particularly its high quantum yield ( Q Y ) of 0.94% in the NIR-II window. This compound is encapsulated with DSPE-PEG 2000 to create PTCBT-CN253 nanoparticles (NPs), which demonstrate excellent biocompatibility. When subjected to 808 nm laser irradiation, 4T1 cancer cells coincubated with PTCBT-CN253 NPs exhibit significant ROS generation and release substantial heat, leading to the effective in vitro eradication of the 4T1 cells. Following intravenous administration into 4T1 tumor-bearing mice, PTCBT-CN253 NPs accumulate at the tumor site, facilitating tumor visualization through NIR-II fluorescence imaging. The growth of 4T1 tumors in mice treated with PTCBT-CN253 NPs and NIR laser irradiation is significantly inhibited, and staining results indicate that the treatment has no adverse effects.