Improving the Intracellular Drug Concentration in Lung Cancer Treatment through the Codelivery of Doxorubicin and miR-519c Mediated by Porous PLGA Microparticle.
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 μm), 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.
Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University , Changchun 130012, China.
Di
D
Wu
Innovative Drug Research Centre, School of Pharmacy, Chongqing University , Chongqing 401331, China.
Chenhui
C
Wang
Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University , Changchun 130012, China.
Jiebing
J
Yang
Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University , Changchun 130012, China.
Hao
H
Wang
Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University , Changchun 130012, China.
Haobo
H
Han
Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University , Changchun 130012, China.
Aijun
A
Zhang
Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University , Changchun 130012, China.
Yan
Y
Yang
Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University , Changchun 130012, China.
Quanshun
Q
Li
D000072283:A549 Cells; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D008175:Lung Neoplasms / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D053719:Tandem Mass Spectrometry
C546194:MIRN519 microRNA, human; D035683:MicroRNAs; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004317:Doxorubicin; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9
ABCG2; cell proliferation; doxorubicin; lung cancer; miR-519c; porous microparticle