多肽自组装研究对药物和基因的控制释放、生物传感、组织工程等领域有重要意义，然而多肽自组装技术仍面临很多挑战。譬如，由于多肽的自荧光集中于紫外不可见光范围，限制了其自组装体系在生物成像等领域的应用。申请人前期的研究工作表明，基于生物荧光蛋白的机理，通过有序的多肽自组装可以生成具有蓝色荧光的多肽纳米颗粒，并对癌细胞进行荧光成像诊断分析和实时监测药物的递送和释放。本项目拟在前期工作基础上尝试应用不同氨基酸序列的多肽，同时引入有机/水相混合溶剂体系，通过对氨基酸序列和自组装条件的优化，合成具有可控荧光的多肽自组装体系，并对食道癌进行体内检测成像和实时跟踪药物的靶向递送。同时探索多肽自组装体系的结构信息和光学性质的关系，阐明此类结构诱导荧光的机制，为设计新型集检测、成像和治疗于一体的生物功能材料奠定理论基础。

Studies on peptide self-assembly are significant to biomedical research areas, such as controlled drug and gene release, biosensing, tissue engineering, etc. However, there are still many technical challenges for peptide self-assembly. Among these challenges, limited intrinsic ultraviolet invisible fluorescence of peptides restricts the applicability of peptide self-assemblies as productive and efficient bioimaging probes. Motivated by the extensive work on green fluorescent protein (GFP), we combined concepts from peptide self-assembly and GFP molecular engineering to create simple dipeptide self-assembled nanoparticles that mimic the optical features of GFP-derived proteins. We also showed that these visible fluorescent dipeptide self-assembled nanoparticles can be used for targeted cellular imaging and real-time drug release monitoring. Based on our previous work, we plan to synthesize the peptide self-assembly nanosystems with controllable fluorescence properties. Specifically, we will build up a library of peptides with various amino acids sequence and introduce the organic solvents as reaction environments for peptide self-assembly. The experimental parameters including temperature, pressure and solvent polarity will be also optimized for visible even near-infrared fluorescence. Afterwards, the fluorescent peptide self-assembly nanosystem will be validated for in vivo esophageal cancer imaging at different tumor stages, including primary solid tumor, earlier carcinoma and metastasis, and tracking the delivery efficacy of drugs. Meanwhile, through discovering the relationship between the structure and optical properties of peptide self-assembly nanosystems, we will try to unveil the underlying principles of the structure induced fluorescence. This study will extend the category of peptide self-assembly nanosystems with optical properties to develop the biocompatible nanoplatform for detection, imaging and therapeutic applications.