酶敏感多肽胶束的构建及其向T细胞递送药物的可行性研究

目的 构建包载芳烃受体抑制剂CH223191的酶敏感多肽胶束并对其进行表征,初步评估此多肽胶束向T细胞递送药物的可行性。方法 采用固相合成法合成了序列为stearyl-HHHRRRRRPLGLAGK-(Mal)的多肽(SHRP)。制备了载药胶束SHRP-CH,测定了其粒径、载药量、临界胶束浓度等,评价其细胞毒性及免疫原性,并使用流式及激光共聚焦考察了CD8⁺T细胞对胶束的摄取效率。结果 SHRP-CH的粒径为(133.8±7.4)nm,酶处理后粒径减少为(92±5.8)nm,载药量和包封率分别为(7.1±1.2)%、(67.7±2.3)%,酶解前后的胶束均具备较低的细胞毒性;CD8⁺T细胞摄取实验证实了此胶束体系向T细胞递送药物的可行性。结论 SHRP多肽酶敏感胶束体系具有较好的载药能力及低细胞毒性,有希望成为T细胞药物递送的潜在载体。

Construction of Enzyme-Sensitive Polypeptide Micelles and Feasibility of Drug Delivery to T Cells

OBJECTIVE To construct and characterize an enzyme-sensitive poly-peptide micelles which carrying the aromatic hydrocarbon receptor inhibitor CH223191, and preliminary evaluate its feasibility of delivering drugs to T cells. METHODS The peptide monomer SHRP was synthesized by solid-phase synthesis and the drug-loaded micelle SHRP-CH was prepared. Its particle size, drug loading, critical micelle concentration, cytotoxicity and immunogenicity etc. were measured. Flow cytometry and laser confocal were used to investigate the uptake efficiency of micelles into CD8⁺T cells. RESULTS The particle size of SHRP-CH was (133.8±7.4) nm, the particle size reduced to (92±5.8) nm after enzyme treatment; drug loading and encapsulation rate were (7.1±1.2)% and (67.7±2.3)%, micelles before and after enzymatic hydrolysis both have low cytotoxicity; CD8⁺T cell uptake experiments confirmed the feasibility of this micelle system to deliver drugs to T cells. CONCLUSION SHRP peptide micelle system has good drug-carrying capacity and low cytotoxicity, and is expected to be a potential carrier for T-cell drug delivery.