Abstract
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 ((1)O(2)), 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 (1)O(2), 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.