Dual Roles of Metal-Organic Frameworks as Nanocarriers for miRNA Delivery and Adjuvants for Chemodynamic Therapy.
Huaixin ZhaoTaotao LiChi YaoZi GuChunxia LiuJiahe LiDayong YangPublished in: ACS applied materials & interfaces (2021)
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.
Keyphrases
- metal organic framework
- induced apoptosis
- long non coding rna
- cancer therapy
- mouse model
- drug delivery
- reactive oxygen species
- long noncoding rna
- genome wide
- endoplasmic reticulum stress
- poor prognosis
- stem cells
- oxidative stress
- signaling pathway
- binding protein
- risk assessment
- dna methylation
- drug release
- copy number
- smoking cessation