期刊
MOLECULAR PHARMACEUTICS
卷 13, 期 11, 页码 3925-3933出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.6b00702
关键词
porous microparticle; doxorubicin; miR-519c; ABCG2; cell proliferation; lung cancer
资金
- Natural Science Foundation of China [81373344, 81473142, 81673502]
- Science & Technology Department of Jilin Province [20140101140JC]
- Education Department of Jilin Province [2015469]
- Frontier Interdiscipline Program of Norman Bethune Health Science Center of Jilin University [2013105014]
- Graduate Innovation Program of Jilin University [2016149]
Porous PLGA microparticle for the coencapsulation of doxorubicin and miR-519c was successfully constructed through the water-oil-water emulsion solvent evaporation method, using ammonium bicarbonate as a porogen. It has been characterized with high porous surface, adaptive aerodynamic diameter (<10 mu m), favorable drug loading, and sustained release profile. The release supernatant exhibited a higher inhibition of cell proliferation than those from porous PLGA microparticles harboring a single component (doxorubicin or miR-519c), attributing to the enhanced induction of cell apoptosis and cell cycle arrest at S phase. Finally, the improved intracellular concentration of doxorubicin was elucidated by flow cytometry and liquid chromatography with tandem mass spectrometry, owing to the knockdown of drug transporter ABCG2 by miR-519c. Overall, the porous PLGA microparticle combining chemotherapy and gene therapy could facilitate the antitumor efficacy and reduce the side effects, and thus, it is potential to be used as a sustained release system for lung cancer treatment via pulmonary administration.
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