Disulfiram-loaded porous PLGA microparticle for inhibiting the proliferation and migration of non-small-cell lung cancer.
In this study, poly(lactic-co-glycolic acid) (PLGA) was used as a carrier to construct disulfiram-loaded porous microparticle through the emulsion solvent evaporation method, using ammonium bicarbonate as a porogen. The microparticle possessed highly porous surface, suitable aerodynamic diameter for inhalation (8.31±1.33 µm), favorable drug loading (4.09%±0.11%), and sustained release profile. The antiproliferation effect of release supernatant was detected through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay using non-small-cell lung cancer A549 as a model, with only 13.3% of cell viability observed for the release supernatant at 7 days. The antiproliferation mechanism was elucidated to be associated with the enhanced induction of cell apoptosis and cell cycle arrest at S phase through flow cytometry and Western blotting analysis. Finally, wound healing and transwell migration assay showed that they could efficiently inhibit the cell migration. These results demonstrated that disulfiram-loaded porous PLGA microparticle could achieve favorable antitumor efficiency, implying the potential of treating non-small-cell lung cancer in a pulmonary administration.
Department of Urology, First Hospital of Jilin University; Innovative Drug Research Centre, School of Pharmacy, Chongqing University, Chongqing.
Chenhui
C
Wang
Department of Urology, First Hospital of Jilin University; Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, People's Republic of China.
Jiebing
J
Yang
Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, People's Republic of China.
Haobo
H
Han
Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, People's Republic of China.
Jiawen
J
Chen
Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, People's Republic of China.
Yudi
Y
Wang
Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, People's Republic of China.
Quanshun
Q
Li
Department of Urology, First Hospital of Jilin University.
Yanbo
Y
Wang
D000280:Administration, Inhalation; D000427:Alcohol Deterrents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000473:pathology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004221:Disulfiram / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology*; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016062:Porosity; D014407:Tumor Cells, Cultured
D000427:Alcohol Deterrents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004221:Disulfiram
antimigration; antiproliferation; disulfiram; non-small-cell lung cancer; poly(lactic-co-glycolic acid); porous microparticle