期刊
ACS APPLIED MATERIALS & INTERFACES
卷 13, 期 5, 页码 6034-6042出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.0c21006
关键词
metal-organic framework; microRNA delivery; chemodynamic therapy; gene therapy; triple-negative breast cancer
资金
- National Natural Science Foundation of China [21621004, 21704074]
- Ministry of Science and Technology of China (National Key Technology Research and Development Program) [2018YFA0902300]
- Tianjin Natural Science Foundation (Basic research plan) [18JCJQJC47600]
- China Postdoctoral Science Foundation [2019M651029]
This study reveals the dual roles of metal-organic framework nanoparticles in miRNA delivery and chemodynamic therapy, demonstrating high efficacy in synergistic gene/chemodynamic therapy.
MicroRNA (miRNA) represents a promising class of therapeutic nucleic acid drugs, while delivery challenges remain that impede the advancement of miRNA therapy, largely because of in vivo instability and low delivery efficiency. Herein, we discover the dual roles of metal-organic framework (MOF) nanoparticles (ZIF-8) as nanocarriers for miRNA delivery and adjuvants for chemodynamic therapy. The miR-34a-m@ZIF-8 complex demonstrated efficient cellular uptake and lysosomal stimuli-responsive miRNA release. Zn2+ triggered the generation of reactive oxygen species, which consequently induced apoptosis of tumor cells. Released miR-34a-m led to a remarkable decrease in expression of Bcl-2 at both mRNA and protein levels and enhanced cancer cell apoptosis. In vivo experiments showed high efficacy of using miR-34a-m@ZIF-8 to suppress tumor growth via synergistic gene/ chemodynamic therapy in a mouse model of triple-negative breast cancer. Our work demonstrates MOFs as a promising nanoplatform for efficient synergetic gene/chemodynamic therapy.
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