微环境靶向/响应纳米颗粒介导新型乳源抗菌肽lactoferrin 96用于新生儿感染防治的应用基础研究

多肽是母乳防治新生儿感染性疾病的重要活性成分，具有重要的临床研究价值。lactoferrin 96是从早产儿母乳中发现的一条新型多肽，前期实验已证实该多肽对新生儿常见致病菌S. aureus、E. coli、P. aeruginosa、K. pneumoniae均具有杀伤作用。但其在临床转化上，仍然面临抗菌机制不明确、无靶向性、易被蛋白酶水解等问题。针对此，本项目拟在前期研究的基础上，进一步论证lactoferrin 96抗新生儿常见致病菌功能并揭示其作用机制；构建能靶向且响应感染微环境，从而释放lactoferrin 96的纳米颗粒；通过体内外实验，分别评估所构建纳米颗粒介导lactoferrin 96对新生儿常见致病菌的抗菌效果以及对新生大鼠NEC、肺炎模型的治疗作用和生物安全性。本项目若顺利完成，将加快lactoferrin 96临床转化速度，为新生儿感染防治提供潜在的新型干预手段。

Peptides are important active components of breast milk in the prevention and treatment of neonatal infectious diseases, and have great clinical research value. As one of them, the lactoferrin 96 has been found recently and confirmed that it could kill common newborn infection bacteria (e.g. S. aureus, E. coli, P. aeruginosa, K. pneumonia etc.) in previous experiments. However, to achieve the clinical transformation of it, there are still some problems needed to be overcome, such as unclear antibacterial mechanism, non-targeting, and easy hydrolysis by proteases. To this end, in the study, we plan to further investigate its broad-spectrum antibacterial activity and reveal the antibacterial mechanism of lactoferrin 96 in vitro based on previous studies, and construct nanoparticles with the ability to microenvironment targeted/responsive release lactoferrin 96. After that, a series of assessments of the lactoferrin 96-loaded nanoparticles will be done, including the antibacterial effects on common newborn infection bacteria in vitro, and the therapeutic effect and biosafety of the nanoparticles in NEC and pneumonia neonatal rat mode. If this project is completed, it will undoubtedly speed up the clinical transformation of lactoferrin 96 and provide a new intervention for the prevention and treatment of neonatal infection.