军事医学2026，Vol.50Issue(3)：161-169,9.DOI:10.7644/j.issn.1674-9960.2026-00006
正电改构铁蛋白纳米颗粒增强腺病毒载体细胞递送效率
Positively charged ferritin nanoparticles enhance cellular delivery efficiency of adenovirus vectors
摘要
Abstract
Objective To develop positively charged human ferritin nanoparticles capable of modulating the surface properties of adenovirus vectors via electrostatic interaction-mediated self-assembly in order to enhance the cellular delivery efficiency of adenovirus vectors.Methods Based on structure-guided rational design,combinatorial amino acid mutations were introduced into wild-type human ferritin heavy chain(hF-wt)to generate a panel of positively charged ferritin mutants[(+)hFm].The particle size and electrostatic binding capacity of(+)hFm were characterized using dynamic light scattering(DLS)and agarose gel electrophoresis,respectively,to identify the optimal(+)hFm that could self-assemble into nanoparticles and exhibit a high affinity for negatively charged biomacromolecules.Furthermore,the properties of the complex formed by the adenovirus type 5 vector(Ad5)and(+)hFm[Ad5@(+)hFm]were determined.The efficacy with which target transgene expressions were enhanced and the potential cytotoxicity of Ad5@(+)hFm were subsequently evaluated in HeLa cells.Results The positively charged ferritins constructed by combinatorial amino acid mutations successfully self-assembled into nanoparticles with size distributions ranging from 10 to 70 nm.Among these mutants,(+)hFm-2 showed strong electrostatic binding to plasmid DNA at a migration retardation rate of up to 95.59%.At a molar ratio of 1∶1000[Ad5 to(+)hFm-2],the two components formed a complex with modulated surface properties,which significantly improved Ad5-mediated transgene expressions in the cellular model without inducing detectable cytotoxicity.Conclusion The positively charged engineered ferritin variant(+)hFm-2 can efficiently bind to Ad5 via electrostatic interaction,enhance Ad5-mediated transgene expressions,and possess high biocompatibility.关键词
人源铁蛋白/正电改构/静电结合/腺病毒载体/细胞递送Key words
human ferritin protein/positively charged engineering/electrostatic interaction/adenoviral vector/cellular delivery分类
生物科学引用本文复制引用
王迪,李纪宏,张军,徐俊杰,杨益隆..正电改构铁蛋白纳米颗粒增强腺病毒载体细胞递送效率[J].军事医学,2026,50(3):161-169,9.基金项目
国家自然科学基金面上项目(82171818) （82171818）
