期刊
MOLECULAR PHARMACEUTICS
卷 13, 期 5, 页码 1723-1730出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.6b00311
关键词
zinc oxide nanoparticles; doxorubicin; pH-responsive; drug resistance; drug delivery
资金
- Chinese Natural Science Foundation [31430031]
- National Distinguished Young Scholars grant [31225009]
- State High-Tech Development Plan [2012AA020804, SS2014AA020708]
- Chinese Academy of Sciences [XDA09030301]
- BIC, Chinese Academy of Science [121D11KYSB20130006]
Multidrug resistance (MDR) of cancer is a challenge to effective chemotherapeutic interventions. The stimulus-responsive drug delivery system (DDS) based on nanotechnology provides a promising approach to overcome MDR. Through the development of a doxorubicin delivery system based on zinc oxide nanomaterials, we have demonstrated that MDR in breast cancer cell line can be significantly circumvented by a combination of efficient cellular uptake and a pH-triggered rapid drug release due to degradation of nanocarriers in acidic environment. Doxorubicin and zinc oxide nanoparticles, compared with free doxorubicin, effectively enhanced the intracellular drug concentration by simultaneously increasing cell uptake and decreasing cell efflux in MDR cancer cells. The acidic environment-triggered release of drug can be tracked real-time by the doxorubicin fluorescence recovery from its quenched state. Therefore, with the combination of therapeutic potential and the capacity to track release of drug in cancer cells, our system holds great potential in nanomedicine by serving dual roles of overcoming drug resistance and tracking intracellular drug release from the DDS.
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