烟台大学学报（自然科学与工程版）2025，Vol.38Issue(3)：300-307,8.DOI:10.13951/j.cnki.37-1213/n.240502
肿瘤微环境响应型IL-12前体蛋白mRNA脂质纳米粒抗肿瘤研究
Anti-tumor Effects of Tumor Microenvironment-Responsive IL-12 Precursor Protein mRNA Lipid Nanoparticles
摘要
Abstract
To address the issues of poor anti-tumor effects and serious immunotoxicity of interleukin-12(IL-12),this study used IL-12β1 receptor as a"protective domain"to connect to the IL-12 precursor structure through a tumor microenvironment(TME)-specifically hydrolyzed peptide segment,designed an IL-12 precursor protein mR-NA(Pro-IL-12 mRNA)that can be specifically cleaved and released in the TME,and constructed the lipid nanop-articles(Pro-IL-12 LNPs)by physically encapsulating them with ionizable lipids.The nanoparticles prepared via microfluidic process showed a homogeneous spherical structure,with a particle size of(93.07±1.02)nm,a PDI of 0.18±0.05,and a Zeta potential of(3.13±0.70)mV and good stability.In vivo pharmacodynamic studies showed that the tumor inhibition rate of Pro-IL-12 LNPs was 64.0％in the MC38 tumor-bearing mouse model,which increased to 85.9％after combination therapy with anti-PD-1 monoclonal antibody.The tumor-suppressive effect and survival time were significantly enhanced,and the mice exhibited good tolerance with no significant differences in body weight between the groups.Further safety studies were carried out to detect inflammatory cyto-kines and hepatotoxicity indexes in serum after administration of the drug to healthy mice,combined with his-topathological section analyses,which showed that Pro-IL-12 LNPs reduced IL-12-induced immunotoxicity without significant liver injury,indicating a favorable safety profile.In conclusion,the precursor protein mRNAs construc-ted in this study for TME-responsive release provide a theoretical basis for the development of new strategies for effi-cient and low-toxicity IL-12 delivery.关键词
白细胞介素12/前体蛋白mRNA/脂质纳米颗粒/免疫治疗/抗肿瘤作用Key words
interleukin-12/precursor protein mRNA/lipid nanoparticles/immunotherapy/anti-tumor effect分类
医药卫生引用本文复制引用
郭婷,于文君,杜雅婷,李燕,付元磊,王爱萍..肿瘤微环境响应型IL-12前体蛋白mRNA脂质纳米粒抗肿瘤研究[J].烟台大学学报（自然科学与工程版）,2025,38(3):300-307,8.基金项目
山东省自然科学基金资助项目(ZR2023MC121). （ZR2023MC121）
