Cisplatin-coordinated copolythiophene for synergistic chemotherapy and sonodynamic therapy of tumor

Sonodynamic therapy (SDT) is a novel cancer treatment type showing the advantages of high tissue penetration ability, non-invasion, low systemic toxicity, and high selectivity. However, SDT depends on ultrasound (US) irradiation; once US is turned off, the sonosensitizer will stop producing reactive oxygen species (ROS). Moreover, most sonosensitizers generate oxygen-dependent ROS, that is, singlet oxygen (¹O₂), significantly limiting the therapeutic effect of SDT in treating deep and hypoxic tumor. Therefore, combining SDT with other treatment modalities is essential. Here, we designed and synthesized a series of cisplatin-coordinated copolythiophenes (CPT-Pts), simultaneously generating ¹O₂, superoxide anion, and hydroxyl radicals for synergistic chemotherapy and SDT of tumor. The sonodynamic toxicity and cytotoxicity of CPT-Pts were accurately regulated by tuning the monomer ratio of the polythiophene. This copolymerization strategy avoids the side effects originating from the high-dose chemotherapy drug while making up for limiting SDT relying on ultrasonic activation, effectively inhibiting cancer cells and tumors.