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

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.

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。

光动力治疗是一种高效的肿瘤（特别是浅表性肿瘤）治疗方式，它具有多重优势如高时空选择性及非侵袭性。光动力治疗领域，肽自组装材料在光敏药物递送及生物应用方面发挥着至关重要的作用，然而，他们通常面临着一些方面的挑战，如结构调控、纳米尺寸、长循环寿命等。在本项目中，我们受生物分子仿生的启发，将寡肽与光敏剂有机结合制备得到新型递送平台用于光动力肿瘤治疗。我们采用分子模拟与理论模型等手段深入研究了寡肽与光敏药物之间的组装机制。同时，我们监测了超分子组装过程并对组装结构进行了研究，实现了纳微结构的可控组装和制备。接下来，我们对所制备的光动力治疗药物进行了相关研究，包括体内外的可控释放、光毒性及暗毒性以及肿瘤细胞的选择性、靶向性及抗肿瘤效果等。本项目所制备的肽基纳米材料具有高的光敏剂装载效率、可控的释放性能。同时，也为光动力治疗药物提供了新的研究思路。