Journal
ACS NANO
Volume 5, Issue 12, Pages 9788-9798Publisher
AMER CHEMICAL SOC
DOI: 10.1021/nn2033105
Keywords
multidrug resistance; hollow mesoporous silica nanoparticles; pore size; drug delivery; doxorubicin
Categories
Funding
- National Basic Research Program of China [2010CB934000, 2009CB930304, 2012CB932500]
- National Natural Science Foundation of China [30925041, 50823007]
- Science and Technology Commission of Shanghai [10430712800]
- Science Foundation for Youth Scholar of State Key Laboratory of High Performance Ceramics and Superfine Microstructures [SKL201001]
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In this work, hollow mesoporous silica nanoparticles (HMSNs) with three pore sizes were manufactured to control the drug release rate, and the biological roles of these HMSNs were evaluated in multidrug-resistant (MDR) cancer cells. As novel pore-size-controllable inorganic materials, HMSNs showed negligible cytotoxicity and efficient cellular uptake toward drug-sensitive MCF-7 and drug-resistant MCF-7/ADR cells. Doxorubicin (DOX)-loaded HMSNs (DMSNs) not only demonstrated effective drug loading and a pH-responsive drug release character but also exhibited pore-size-dependent and sustained drug release performance in both in vitro and intracellular drug release experiments. In addition, DMSNs exhibited pore-size-dependent anticancer activity against MCF-7/ADR cells. DMSNs with larger pore size could mediate more cellular uptake of DOX and faster intracellular drug release, which led to more intracellular drug accumulation and stronger MDR-reversal effects. The MDR-overcoming mechanism could be due to the efficient cellular uptake, P-gp inhibition, and ATP depletion. These results demonstrate that HMSNs could be a very promising drug delivery system for pore-size-controllable drug release and cancer MDR reversion.
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