Journal
MOLECULAR PHARMACEUTICS
Volume 13, Issue 8, Pages 2749-2759Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.6b00352
Keywords
mesoporous silica nanoparticles; dual delivery; cancer stem cells; shABCG2
Funding
- National Natural Science Foundation of China [81372893, 91442121]
- outstanding Youth Foundation for the Zheng Zhou University [51999231]
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Cancer stem cells (CSCs) are responsible for cancer drug resistance with high expression of ABCG2, which pumps the internalized chemotherapeutic out to escape drug-induced cytotoxicity. Here, we established a functionalized mesoporous silica nanoparticle (MSN) system to deliver shABCG2 and doxorubicin (Dox) synergistically. With excellent cell uptake and endosomal escape capacities, the dual-delivery carriers internalized shABCG2 and Dox into CSCs efficiently. ABCG2 depletion increased intracellular and intranuclear Dox enrichment, drove vigorous Dox-induced cell death, and impaired the self-renewal of CSCs. Additionally, the nanoparticles eliminated tumors efficiently and reduced tumor initiation by CSCs in vivo, with negligible side effects. Our findings suggest that well-designed delivery systems for conventional chemotherapeutic agents are promising for CSC therapy.
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