Cation-π interactions widely exist in biological systems and play important roles in driving the self-assembly of biological molecules, stabilizing protein structures, and mediating molecular recognitions. Herein, a novel bioinspired poly(cation-π) micelles drug delivery platform is designed and constructed, based on the block copolymers with random cationic-aromatic sequences (amphiphilic cation-π polymer). Compared to the polymeric micelles formed by conventional amphiphilic block copolymers which are commonly limited to hydrophobic drugs loading, the engineered poly(cation-π) micelles can serve as a universal nanocarrier for a wide variety of hydrophobic and hydrophilic drugs with π-structure. It is found that due to the strong cation-π interactions integrated in the core of poly(cation-π) micelles, this nanosystem performs improved structural stability and higher drug loading capability. Especially, in the oxidation-responsive poly(cation-π) micelles as proof-of-concept, the process of stimuli-induced drug release is found significantly accelerated under the biologically relevant level of H₂O₂ in tumor microenvironment. Furthermore, the mechanism of cation-π interaction enhanced H₂O₂-sensitivity of poly(cation-π) micelles is proposed, and the improving anti-tumor efficacy is demonstrated in both in vitro and in vivo models. This work broadens the construction strategy of polymeric micelles and offers a universal drug delivery platform for efficient tumor chemotherapy.

阳离子-π相互作用广泛存在于生物系统中，在驱动生物分子的自组装、稳定蛋白质结构和介导分子识别等方面发挥着重要作用。在此，基于具有随机阳离子-芳族序列的嵌段共聚物（两亲阳离子-π聚合物），设计和构建了一种新型的仿生聚（阳离子-π）胶束药物递送平台。与传统的两亲嵌段共聚物形成的聚合物胶束（通常仅限于疏水性药物负载）相比，工程聚（阳离子-π）胶束可以作为具有π-结构的各种疏水性和亲水性药物的通用纳米载体。发现由于聚（阳离子-π）胶束核心中集成的强阳离子-π相互作用，该纳米系统具有更高的结构稳定性和更高的载药能力。特别是在作为概念验证的氧化响应性聚（阳离子-π）胶束中，发现在 H 的生物学相关水平下，刺激诱导的药物释放过程显着加速₂ O ₂在肿瘤微环境中。此外，提出了阳离子-π相互作用增强聚(阳离子-π)胶束对H ₂ O ₂敏感性的机制，并在体外和体内模型中证明了其提高的抗肿瘤功效。这项工作拓宽了聚合物胶束的构建策略，并为有效的肿瘤化疗提供了一个通用的药物递送平台。