期刊
BIOACTIVE MATERIALS
卷 11, 期 -, 页码 1-14出版社
KEAI PUBLISHING LTD
DOI: 10.1016/j.bioactmat.2021.10.007
关键词
Core-shell nanoparticles; Non-viral gene delivery; Precise gene editing; CTCF; Metastatic breast cancer
资金
- Natural Science Foundation of Beijing Municipality [7181004]
- National Natural Science Foundation of China [81874303]
This study developed a targeted core-shell nano-particles carrying dual plasmids for precise gene insertion to treat metastatic breast cancer, and found the associated inhibitory mechanism.
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 nano-particles (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 gamma GTP-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, fol-lowed 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.
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