专业外语教学（吉林大学）140710-Manuscript for PLGA microparticles.docVIP

Combination of doxorubicin-based chemotherapy and polyethylenimine/p53 gene therapy for the treatment of lung cancer using porous PLGA microparticles Xiaozheng Shi a,c, Chunjie Li a,c, Sai Gao a,c, Lingfei Zhang a,c, Haobo Han a,c, Jianxu Zhang a,c, Wei Shi a,b,c,*, Quanshun Li a,b,c,* a Key Laboratory for Molecular Enzymology and Engineering, the Ministry of Education, Jilin University, Changchun 130012, China b National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun 130012, China c School of Life Sciences, Jilin University, Changchun 130012, China *Corresponding author. Tel.: +86-431 Fax: +86-431 E-mail address: quanshun@jlu.edu.cn (Q. Li); shiw@jlu.edu.cn (W. Shi). Abstract In this study, porous PLGA microparticles for the co-delivery of doxorubicin and PEI25K/p53 were successfully prepared by the water-oil-water emulsion solvent evaporation method, using ammonium bicarbonate as a porogen. The porous microparticles were obtained with a mean diameter of 22.9±11.8 μm as determined by laser scattering particle size analysis. The particles’ surface porous morphology and distributions of doxorubicin and p53 were systematically characterized by scanning electron microscopy, flow cytometry, fluorescence microscopy and confocal laser scanning microscopy, revealing that doxorubicin and the plasmid were successfully co-encapsulated. Encapsulation efficiencies of 88.2±1.7% and 36.5±7.5% were achieved for doxorubicin and the plasmid, respectively, demonstrating that the porous structure did not adversely affect payload encapsulation. Microparticles harboring both doxorubicin and PEI25K/p53 exhibited enhanced tumor growth inhibition and apoptosis induction compared to those loaded with either agent alone in A549 human lung adenocarcinoma cells. Overall, the porous PLGA microparticles provide a promising anticancer delivery system for combined chemotherapy and gene therapy, and have great potential as a tool for sustained local