高分子化疗和基因药物纳米共输送体系用于癌症治疗受到化疗药物担载量低、释放不可控，基因药物内涵体逃逸与卸载困难等问题限制，开发新型高分子纳米共输送体系同时实现两类药物的高效担载和可控释放具有非常重要的意义。本项目创新性地将抗癌“前药”，四价光敏铂化合物，作为光敏剂和疏水组分引入高分子主链，制备了一类从紫外光到近红外光敏感的主链含铂聚阳离子；静电复合基因药物后形成的纳米颗粒即可实现联合治疗。该纳米颗粒内吞入癌细胞后，光照下四价光敏铂化合物会释放叠氮自由基破坏内涵体膜实现载体内涵体逃逸；同时还会光还原成二价铂药，诱导载体主链结构迅速崩解，实现光控铂药释放和基因卸载；充分发挥两类药物间协同增效作用，逆转肿瘤耐药性。利用该体系中两类药物同时高效担载和光控释放以及光控波长可调的优势，深入研究其联合治疗效果与协同作用机理，为更高水平的高分子化疗和基因药物纳米共输送体系设计提供理论指导和试验依据。

Polymeric nano-carrier mediated co-delivery of drugs and genes for cancer therapy is limited by low drug loading capacity and uncontrolled release fashion, difficulty for genes’ endosomal escape and unpacking. There is correspondingly a clear incentive to develop new polymeric co-delivery systems for simultaneous high loading capacity and controlled release of both drugs and genes. Anti-cancer prodrugs, photo-activated platinum(IV) complexes, are creatively used as photosensitizers and hydrophobic monomers to prepare photo-sensitive (from UV to NIR light) platinum-backboned polycation for gene delivery. After complexing with gene, the formed nanoparticles are polymeric combination therapy systems. When the nanoparticles were internalized by cancer cells and irradiated with feasible light, photo-activated platinum(IV) complexes would release oxidizing azidyl radicals to assist gene escape from endosomes/lysosomes by membranes disruption, and simultaneously photo-reduction to release active platinum(II) anti-cancer drugs after light-induced fast degradation of the polycation backbones to improve gene unpacking. Then the synergistic effect of platinum drug and gene could be fully realized, resulting in enhanced anticancer efficacy and even cisplatin resistance reversal. Taking advantages of simultaneous high loading capacity and controlled release of both drug and gene, and tunable sensitive wavelengths of the polymeric co-delivery systems, the light-controlled combination therapy efficacy and synergy mechanisms are in-depth studied, providing theoretical guidance and experimental basis for the design of other high-level polymeric nano-carrier mediated co-delivery systems of drugs and genes for cancer therapy.