靶向线粒体的超声驱动多肽材料及其针对前列腺癌的诊疗研究

去势抵抗性前列腺癌由于其激素依赖性和随之产生的耐药性，以及较高的异质性和少血管性，导致药物递送和治疗效率较低。我们前期研究表明线粒体靶向多肽诱导的细胞凋亡能够克服其耐药性;然而由于前列腺肿瘤的增强渗透滞留效应较差，亟待发展新体系实现高效靶向的主动药物递送。本项目拟设计并合成线粒体靶向及超声驱动的多肽聚合物材料，并在超声辅助下开展其针对前列腺癌的诊疗研究：（1）设计合成超声响应性多肽聚合物，并通过自组装获得非对称碗状结构，同时研究其超声驱动机制；（2）对多肽聚合物组装体接枝线粒体靶向ATAP多肽，并开展胞内靶向线粒体的分子机制研究；（3）利用小鼠模型进行超声辅助的体内靶向递送和定点响应性释放的研究。总之，本项目旨在开发具有线粒体靶向和超声驱动功能的多肽聚合物材料，并应用于前列腺癌的精准治疗，具有一定的临床前意义和重要的研究意义。

Due to androgen dependence, drug resistance and high heterogeneity and less vascularization, the drug delivery and therapeutic efficiency of castrate-resistant prostate cancer are relatively low. Our previous studies have demonstrated that mitochondria targeted peptide and its related cell apoptosis could overcome the drug resistance of prostate cancer cells. However, due to the low and inhomogeneous enhanced permeability and retention (EPR) effects of prostate tumor, it is meaningful to develop active targeted drug delivery system. In this project, we intend to design and synthesize mitochondria-targeting and ultrasound propelled peptide assemblies for targeted therapy of prostate cancer: (1) synthesizing ultrasound responsive peptide based polymers, and then self-assembling into asymmetric nanostructure to study the ultrasound propulsion effects and mechanisms; (2) modifying peptide assemblies with ATAP peptide moieties and studying the molecular mechanism of mitochondria targeting effects; (3) conducting in vivo ultrasound guided delivery with targeting efficiency and responsive release. Overall, this project aims to develop mitochondria-targeting and ultrasound propelled peptide assemblies for treatment of prostate cancer with remarkable research and preclinical significance.