叶绿素-多肽衍生物制备及在细菌感染早期检测中的应用研究

Considerable efforts have been devoted to early-stage detection and in vivo imaging of bacterial infections. The challenges remain in this direction are the design and preparation of highly-sensitive, low toxic and infection responsive contrast agents. In this proposal, we plan to construct enzyme responsive chlorophyll-peptide derivatives for photoacoustic imaging contrast agents. The enzyme (caspase-1) responsive peptide coupled with signal molecule (chlorophyll derivatives) using a solid phase peptide synthesis method for infection responsive photoacoustic contrast agents. According to adjust parameters (peptide sequence, length, chemical modification, potential) clarify its biocompatibility, infection responsibility and ability of photoacoustic imaging. In vitro and in vivo modes are designed to study the responsive kinetics of responsibility of chlorophyll-peptide derivatives and caspase-1. The biodistribution, biosafety issues and responsibility will be investigated by using mice models. Altogether, this research proposal aims to develop novel strategies for preparation and application of in vivo infection responsive contrast agents for early-stage bacterial infections diagnose. The successful demonstration of this strategy will open new avenue for infections diagnose in the future.

细菌感染的早期检测以及细菌感染部位的活体成像成为了感染诊疗研究的热点。设计和制备新型灵敏、低毒、感染部位特异性响应的生物成像探针成为了局部感染早期诊疗的核心和瓶颈问题。本项目拟发展酶响应叶绿素-多肽衍生物光声成像探针，通过固相合成法将白介素-1β转换酶响应性多肽与具有光声信号的叶绿素衍生物分子共价联接，制备具有感染响应性的光声成像探针。研究通过对其理化参数（多肽序列顺序、氨基酸长度、化学修饰、电荷等）的控制，揭示其理化参数与生物相容性、感染响应性之间的关系以及成像特性；设计体内外模型，研究叶绿素-多肽衍生物分子与白介素-1β转换酶响应性之间的动力学，为设计与制备感染区域特异性响应的新型光声成像探针提供实验依据和理论基础；研究叶绿素-多肽衍生物体系的体内分布、安全性、响应性，并对其在感染部位的光声成像性能进行初步探讨。本项目拟为发展新型局部感染早期检测技术提供新方法、新思路和新途径。