基于特异性多肽LCP8和巨噬细胞膜组分的双重靶向载体递送HSV-TK基因用于肝癌靶向治疗的实验研究

批准号:
82003258
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
段醒妹
依托单位:
学科分类:
肿瘤生物治疗
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
段醒妹
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中文摘要
基因治疗技术为肝癌的治疗提供了新选择。但肝癌特异性药物递送手段的不足,限制了肝癌基因治疗的发展和应用。因此,急需开发具有高选择性的肝癌靶向基因递送策略。申请人基于通过噬菌体展示技术新筛选获得的肝癌细胞特异性多肽LCP8,结合前期自主开发的DMP非病毒基因导入载体,创新性地加以巨噬细胞膜组分修饰,成功构建了一种针对肝癌细胞的新型双重靶向基因递送载体LCP8-m-DMP,其靶向效果已得到初步验证。更重要的是,申请人已成功筛选出LCP8多肽在肝癌细胞表面的特异性蛋白受体候选分子。上述成果未见相关报道。本研究中,我们将进一步评估LCP8-m-DMP载体的靶向能力,深入分析其靶向分子机制,同时通过静脉途径对已在肝癌治疗临床研究中充分验证的HSV-TK自杀基因进行体内系统性递送,从而获得一种创新的肝癌双重靶向基因治疗手段。该题目具有良好可行性,将为肝癌基因治疗新策略的开发提供基础。
英文摘要
The rapid development of gene therapy technology has provided novel strategy for liver cancer treatment. However, the efficacy and safety of systemically administration-based liver cancer gene therapy are high limited by lacking specific delivery method. In previous work, we have successfully developed a novel dual-liver cancer cell targeted gene delivery system LCP8-m-DMP based on a newly discovered caner specific peptide and macrophage membrane composition. The two novel targeting motifs are supported by our previously constructed DMP cationic nanoparticle. The in vivo targeting ability of this vector has been approved. Moreover, two candidates of potential LCP8-specific transmembrane receptors have already been uncovered. In this program, we will continue our work in the study about the targeting mechanism. Meanwhile, we intend to perform an in vivo liver cancer therapy with LCP8-m-DMP delivered HSV-TK gene, developing a new targeted liver cancer gene therapy strategy. This study is well designed and practicable; it will contribute to the discovery of new therapeutic strategy for liver cancer.
期刊论文列表
专著列表
科研奖励列表
会议论文列表
专利列表
DOI:10.1038/s41392-022-01249-8
发表时间:2022-12-05
期刊:SIGNAL TRANSDUCTION AND TARGETED THERAPY
影响因子:39.3
作者:Lei, Sibei;Chen, Xiaohua;Wu, Jieping;Duan, Xingmei;Men, Ke
通讯作者:Men, Ke
DOI:10.3390/pharmaceutics14010162
发表时间:2022-01-11
期刊:Pharmaceutics
影响因子:5.4
作者:Chen X;Zhou B;Gao Y;Wang K;Wu J;Shuai M;Men K;Duan X
通讯作者:Duan X
DOI:10.1002/adfm.202204342
发表时间:2022-08-15
期刊:ADVANCED FUNCTIONAL MATERIALS
影响因子:19
作者:Lei, Sibei;Chen, Xiaohua;Duan, Xingmei
通讯作者:Duan, Xingmei
DOI:10.2147/ijn.s357702
发表时间:2022
期刊:International journal of nanomedicine
影响因子:8
作者:
通讯作者:
DOI:10.1016/j.jconrel.2022.02.022
发表时间:2022-02
期刊:Journal of controlled release : official journal of the Controlled Release Society
影响因子:--
作者:Sibei Lei;Yan Gao;Jingmei Li;Xiaohua Chen;Weilin Zhou;Jieping Wu;Pingchuan Ma;Ke Men;
通讯作者:Sibei Lei;Yan Gao;Jingmei Li;Xiaohua Chen;Weilin Zhou;Jieping Wu;Pingchuan Ma;Ke Men;
国内基金
海外基金
