聚乙烯亚胺纳米载体的设计及其在DNA体内外递送中的性能评估

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中图分类号： Q936 文献标志码：A 文章编号：1673-3851（2025）09-0656-08

Reference Format：SUN Jiayi，LU Xiaofeng，SHU Jianhong，etal.Design of polyethyleneimine nanocarriersand evaluationof their performanceinDNAdeliveryinviooandexioJ].Journalof Zhejiang Sci-TechUniversity，202553 （5）：656-663.

Design of polyethyleneimine nanocarriers and evaluation of their performance in DNA delivery in vivo and ex vivo

SUN Jiayi1，2，LU Xiaofeng²，SHU Jianhong1 ，WU Fangli1，JIN Weib01.2 （1. College of Life Sciences and Medicine， Zhejiang Sci-Tech University， Hangzhou 3lOol8，China; 2. Zhejiang Sci-Tech University Shaoxing Academy of Biomedicine， Shaoxing 3l2366，China）

Abstract： Polyethyleneimine（PEI） nanocarriers are widely used for nucleic acid drug delivery，but high cytotoxicity limits their clinical applications. Dioleoyl phosphatidylethanolamine （DOPE） and cholesterol were used to modify PEI with molecular weights of 1.2kDa and 25.0kDa ，and PEI/DNA nanoparticles were prepared by mixing modified PEI with DNA at diferent nitrogen-to-phosphorus ratios. The physicochemical properties，cytotoxicity and transfection efficiency of the nanoparticles were evaluated，and eficient and low-toxicity PEI nanocarriers were screened. The results showed that DOPE and cholesterol modifications significantly reduced the cytotoxicity of PEI/DNA nanoparticles. When the nitrogen-phosphorus ratios were 3 and 5，the modified nanoparticles had an average particle size of about 200nm ，a zeta potential between 5mV and 10mV ，and a dispersion between O.1 and O.2. When the nitrogen-phosphorus ratio was 5， the modified 25.0kDa nanoparticles exhibited the highest DNA in vivo and ex vivo delivery eficiency and low cytotoxicity. This result indicated that auxiliary lipid modification significantly affected the cytotoxicity of the nanoparticles，and the PEI molecular weight and nitrogenphosphorus ratio significantly affected the physicochemical properties and transfection eficiency of the nanoparticles. The nanoparticles prepared by screening the modified 25.0kDa PEI mixed with DNA at a nitrogen-phosphorus ratio of 5 exhibited both high gene delivery eficiency and good biocompatibility， which provided data support for the application of PEI nanocarriers in the field of DNA vaccine delivery.

Key Words：polyethyleneimine；dioleoyl phosphatidylethanolamine；cholesterol；PEI/DNA nanoparticles DNA delivery

0 引言

核酸药物在疾病治疗中应用潜力巨大，但核酸分子的不稳定性及其在内化过程中存在的递送屏障等问题，限制了其在临床上的应用[1-2]。（剩余15400字）