Targeted core-shell nanoparticles for precise CTCF gene insert in treatment of metastatic breast cancer  

作　　者：Jialun Duan Chunjie Bao Ying Xie Haitao Guo Yixuan Liu Jianwei Li Rui Liu Peishan Li Jing Bai Yan Yan Limin Mu Xueqi Li Guiling Wang Wanliang Lu 

机构地区：[1]State Key Laboratory of Natural and Biomimetic Drugs,Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems,And School of Pharmaceutical Sciences,Peking University,Beijing,100191,China [2]Academy for Advanced Interdisciplinary Studies,Peking University,Beijing,100875,China

出　　处：《Bioactive Materials》2022年第5期1-14,共14页生物活性材料（英文）

基　　金：supported by the Natural Science Foundation of Beijing Municipality(Key Grant No.7181004);the National Natural Science Foundation of China(No.81874303).

摘　　要：Clustered regularly interspaced short palindromic repeats(CRISPR)technology emerges a remarkable potential for cure of refractory cancer like metastatic breast cancer.However,how to efficiently deliver the CRISPR system with non-viral carrier remains a major issue to be solved.Here,we report a kind of targeted core-shell nanoparticles(NPs)carrying dual plasmids(pHR-pCas9)for precise CCCTC-binding factor(CTCF)gene insert to circumvent metastatic breast cancer.The targeted core-shell NPs carrying pHR-pCas9 can accomplishγGTP-mediated cellular uptake and endosomal escape,facilitate the precise insert and stable expression of CTCF gene,inhibit the migration,metastasis,and colonization of metastatic breast cancer cells.Besides,the finding further reveals that the inhibitory mechanism of metastasis could be associated with up-regulating CTCF protein,followed by down-regulating stomatin(STOM)protein.The study offers a universal nanostrategy enabling the robust non-viral delivery of gene-editing system for treatment of severe illness.

关 键 词：Core-shell nanoparticles Non-viral gene delivery Precise gene editing CTCF Metastatic breast cancer 

分 类 号：R737.9[医药卫生—肿瘤] R730.5[医药卫生—临床医学]