生物大分子药物递释系统（BDDS）的药效和安全性评价是其实现临床转化的关键，但迄今尚缺乏BDDS药效与安全性评价技术体系，对BDDS理化特性影响其药效和安全性的机理研究十分有限。本课题拟根据生物大分子药物及其BDDS的特点和共性，以载胰岛素、曲妥珠单抗、Cas9及甲胎蛋白等生物大分子药物的BDDS为模型，采用圆二色谱、等温微量热、ELISA、RT-PCR、Western-blot、流式细胞术等技术，在分子、细胞和动物水平上建立针对载蛋白多肽、抗体、核酸和疫苗BDDS的药效评价新方法与技术体系；根据BDDS给药方式和生物大分子药物的特性，建立细胞及动物模型，通过考察BDDS对细胞凋亡、血液生化指标、炎症因子和免疫细胞等的影响，系统评价BDDS在细胞和整体动物水平的安全性，阐明BDDS提高药效的机制，揭示BDDS理化特性与其药效和安全性间的关系，为新型BDDS药效和安全性评价提供理论指导。

The efficacy and safety of biomacromolecular drug delivery systems(BDDS) are keys for clinical translation of biomacromolecular drugs. However, there is no systemic methods currently established to evaluate the efficacy and safety of BDDS, and the influence of physicochemical properties of BDDS on their efficacy and safety is not well-understood. In this project, the efficacy of BDDS will be investigated based on their specific and common characteristics using insulin, herceptin, Cas9, alphafetoprotein and etc as model drugs, and Fourier transform infrared spectroscopy, circular dichroism, isothermal titration calorimetry, ELISA, RT-PCR, Western-blot, flow-cytometry, fluorescence microscopy, animal models with diabetes or cancer will be used to evaluate the efficacy of protein/peptide-, antibody-, nucleic acid- and vaccine-loaded BDDS at molecular, cellular and animal levels. The safety of BDDS will be investigated based on their routes of administration and activities on appropriate cell and animal models, using cellular ROS status, cell apoptosis, blood biochemical parameters, inflammation factors, and activation of immune cells as key indicators for toxicity at cellular and animal levels. This project will demonstrate the mechanism through which the BDDS exert their efficacy and toxicity, reveal the correlation between the physicochemical properties of BDDS with their efficacy and safety, and provide guidelines for the efficacy and safety evaluation of newly developed BDDS.