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 accomplish γGTP-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.