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 syst...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.展开更多
基金supported by the Natural Science Foundation of Beijing Municipality(Key Grant No.7181004)the National Natural Science Foundation of China(No.81874303).
文摘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.
