修饰氯喹脂质体的制备及其对外泌体分泌的影响

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中图分类号：R943 文献标志码：A 文章编号：1671－4652（2025）05-0066-10

ABSTRACT：To investigate theefectsofchloroquineliposomes（CQ-Lips）modifiedwithcationic materialsandcell-penetrating peptides （CPPs）oncellar exosome secretion，modified CQ-Lips composed of soybean phosphatidylcholine，cho lesterol，DOTAP，DOPC，and TAT peptide were prepared using freeze-thaw cycles.The cytotoxicityof cationic materials with varying charge ratios [DOTAP/DOPC （5：0）-（1：4）] ， concentration gradients （7.5，15，30mmol⋅L-1） ，and TAT modification levels （1%-9%） was evaluated via CCK-8 assay. Western blot was employed to quantify exosome secretion under different modification conditions and identifyoptimal parameters.Results demonstrated thatcationic materials exhibited concentration-dependent cytotoxicity，with the 30mmol⋅L-1 group showing significantly reduced cell viability （ P< 0. 01），while no statistical differences were observed among groups with the same concentration （15mmol⋅L-1） ）and varying charge ratios. TAT modification at concentrations 56% significantly decreased cell viability （ P<0.01 ）. The dualmodified CQ-Lips （ 15mmol⋅L-1 cationic material，DOTAP/DOPC 5：0 ; 5% TAT） exhibited superior exosome secretion compared to single-modified groups （ P<0.05; . In conclusion，this study successfully established a novel TAT -cationic co-modified CQ-Lipsdelivery system，which significantly enhanced exosome secretion by optimizing charge parameters and CPP ratios，providing critical experimental insights for advancing high-eficiency exosome production technologies.

KEY WORDs： liposomes; exosome yield; chloroquine;cationic derivatives; cell-penetrating peptides （CPPs）

外泌体是由活细胞分泌的直径为 30～200nm 的脂质双分子层囊泡，其天然携带蛋白质、RNA及脂质等生物活性分子，并具有向受体细胞递送这些分子的独特能力，因而被视为极具潜力的药物递送载体和再生医学无细胞治疗工具[2-4]。（剩余13632字）