Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 10, Issue 26, Pages 22767-22775Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.8b07698
Keywords
combined therapy; controlled release; gene interference; microRNA-31; mesoporous silica nanoparticles
Funding
- Beijing Natural Science Foundation [2172039]
- National Key R&D Program of China [2018YFA0106901]
- National S&T Major Project of China [2018ZX10301201]
- Fundamental Research Funds for the Central Universities, Strategic Priority Research Programs of CAS [XDA12010313]
- Key Research Program of Frontier Sciences, CAS [QYZDB-SSW-SMC028]
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Gene interference-based therapeutics represent a fascinating challenge and show enormous potential for cancer treatment, in which microRNA is used to correct abnormal gene. On the basis of the above, we introduced microRNA-31 to bind to 3'-untranslated region of mtEF4, resulting in the downregulation of its messenger RNA and protein to trigger cancer cells apoptosis through mitochondria-related pathway. To achieve better therapeutic effect, a mesoporous silica nanoparticle-based controlled nanoplatform had been developed. This system was fabricated by conjugation of microRNA-31 onto doxorubicin-loaded mesoporous silica nanoparticles with a poly(ethyleneimine)/hyaluronic acid coating, and drug release was triggered by acidic environment of tumors. By feat of surface functionalization and tumor-specific conjugation to nanoparticles, our drug delivery system could promote intracellular accumulation of drugs via the active transport at tumor site. More importantly, microRNA-31 not only directly targeted to mtEF4 to promote cell's death, but had synergistic effects when used in combination with doxorubicin, and achieved excellent superadditive effects. As such, our research might provide new insights toward detecting high mtEF4 cancer and exploiting highly effective anticancer drugs.
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