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

Yuanyu Tang, E. Pang, Pan Zhu, Qiuxia Tan, Shaojing Zhao, Benhua Wang, Chaoyi Yao, Xiangzhi Song, Minhuan Lan
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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 (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.

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用于肿瘤协同化疗和声动力疗法的顺铂配位共聚噻吩
声动力疗法(SDT)是一种新型癌症治疗方法,具有组织穿透能力强、无创伤、全身毒性低、选择性高等优点。然而,SDT 依赖于超声(US)照射;一旦关闭 US,声纳敏化剂将停止产生活性氧(ROS)。此外,大多数声纳敏化剂都会产生依赖氧的 ROS,即单线态氧(1O2),这大大限制了 SDT 治疗深部和缺氧肿瘤的疗效。因此,将 SDT 与其他治疗方式相结合至关重要。在此,我们设计并合成了一系列顺铂配位共聚噻吩(CPT-Pts),可同时产生 1O2、超氧阴离子和羟基自由基,用于肿瘤的协同化疗和 SDT。通过调整聚噻吩的单体比例,可精确调节 CPT-Pts 的声动力学毒性和细胞毒性。这种共聚策略既避免了大剂量化疗药物带来的副作用,又弥补了依靠超声波激活 SDT 的局限性,有效抑制了癌细胞和肿瘤。
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