刺激响应型仿肽结构线形及三臂星形聚前药共聚物的精密制备及性能研究

肿瘤治疗中，药物分子在病灶部位的有效浓度偏低是降低最终治疗效果的因素之一，具有高选择性、高载药量、以及肿瘤微环境响应性的诊疗一体化纳米试剂便成为了研究热点。本项目拟借助活性聚合手段制备一系列具有刺激响应型仿肽结构线形及三臂星形聚前药共聚物，并对其组装行为及组装体在肿瘤治疗中的潜在应用进行研究。首先，正电荷螺旋链有着与细胞穿膜肽类似的结构，能有效增强组装体与细胞膜磷脂层的相互作用，从而达到促进纳米载体快速、高效穿透细胞膜的目的；其次，聚前药分子链不但能够提高药物分子在血液循环时的稳定性，而且能够选择性在肿瘤细胞内高浓度谷胱甘肽触发下发生断裂，从而释放出原药分子进行化学治疗；此外，聚染料分子链也浓集了近红外分子，在有效提高成像精度的同时，亦能高效进行光热转换进行光声成像和光热治疗，相比于物理包裹的自由小分子有着绝对的优势。本项目研究成果将为肿瘤的早期诊断与治疗提供一种新型的纳米试剂。

In cancer treatment, the low drug loading content always limited their final therapeutic effect. To address this issue, novel therapeutic platforms integrating high selectivity, high drug loading, and tumor microenvironment responsiveness have become a research hotspot. In this project, a series of stimuli-responsive peptide imitating linear and miktoarm terpolymers based polyprodrugs were synthesized through living polymerization. Firstly, the positively charged helical chains adopt a similar structure to cell-penetrating peptides, nanoparticles modified with them could largely enhance their interaction with cell membrane as well as the subsequent endocytosis. Then, poly(prodrug) could maintain the drug stability during blood circulation and extend the circulation time. Upon cellular internalization, the reductive milieu actuated the release of anticancer drugs in their active form, realizing the activation of therapeutic efficacy. Moreover, poly(dye) chains concentrated free dyes, not only improve their stability but also intensify the photothermal conversion, achieving excellent photoacoustic imaging guided synergistic chemo-photothermal therapy. In summary, we believe that this developed platform with several combined advantages could be served as a new encouraging alternative to ablation of tumor tissue.