光敏剂功能化寡肽的自组装:分子设计、结构调控与光动力治疗应用研究

项目名称： 光敏剂功能化寡肽的自组装:分子设计、结构调控与光动力治疗应用研究

项目编号： No.21473208

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 环境科学、安全科学

项目作者： 闫学海

作者单位： 中国科学院过程工程研究所

项目金额： 86万元

中文摘要： 作为生物体系的重要结构单元之一，肽在新材料设计和开发方面具有独特的优势，特别是寡肽由于其结构简单、可灵活设计并且能自组装形成多种纳米结构，在生物医药方面显示了极大的应用潜力。基于此，本项目以对肽分子自组装的理解和认识为基础，将光敏剂（光动力治疗药物）与寡肽分子进行有机结合，设计合成新颖的具有光动力治疗功能的自组装肽分子。深入研究分子结构与自组装行为之间的关系，结合理论模拟等手段阐明分子结构、超分子组装与纳米结构之间的内在关联及组装过程机理，进而实现纳微结构的可控组装和制备。研究自组装纳微结构在细胞或体内的控制释放、光毒性和暗毒性，并进一步研究它们的选择性、靶向性、体内药物毒性和抗肿瘤效果等。通过对光敏剂-肽复合分子组装体系的理解和认识，构筑兼具光敏剂高效负载、有效输送和可控释放于一体的肽基纳米载体，为光动力治疗提供高效和可靠的剂型。

中文关键词： 肽；自组装；光敏剂；结构调控；光动力治疗

英文摘要： Biomimetic or bio-inspired functional materials with ordered organization at micro- or nanoscale, fabricated from peptide building blocks, are of increasing importance thanks to their potential application in biomedicine and nanotechnology. Among all self-assembling peptide building blocks, oligopeptides consisting of several amino acids have been paid much attention due to its simple structure, versatile function, relatively low price and widespread application. In this project, we will combine the self-assembling oligopeptides with photosensitizers for creation of novel delivery nanovectors aiming at photodynamic therapy (PDT) starting from the viewpoint of molecular biomimetics and self-assembly. Connections and mechanisms between molecular structures of oligopeptides, supramolecular architectures and self-assembled nanostructures will be studied in combination with molecular simulation and theory model, to ultimately achieve controlled assembly of micro- or nano-structures. Subsequently, we will investigate the controlled release both in vitro and in vivo, phototoxicity and dark toxicity of peptide-based nanovectors, and further their selectivity, targeting ability, toxicity and antitumor effect etc. Based on the above, we will fabricate peptide-based nanovectors with functions of high-loading of photosensitizers, targeting delivery and controlled release, paving a way for creation of reliable and efficient PDT nanomedicine.

英文关键词： peptide;self-assembly;photosensitizer;structural modulation;photodynamic therapy