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Folate-functionalized and cisplatin loaded polymeric micelles combined with concurrent radiotherapy for the treatment of lung cancer in vitro and in vivo

HUANG Yuxiang WANG Xuanyi LIU Yongbiao WU Yinxia YANG Hang YAO Zhifeng XU Guoping (Department of Radiation Therapy, the First Affilicated Hospital of NJMU, Nanjing 210029, China)  
The tumor-targeting drug delivery system FA-PEG-g-PAsp-CDDP micelles were fabricated from folate-conjugated PEG-graft-α, β-poly [(N-aminoacidyl)-aspartamide] and CDDP. The purpose of this experiment was to test the anti-tumor and radio-sensitizing efficiency of FA-PEG-g-PAsp-CDDP in vitro and in vivo. In vitro, we compared the cytotoxicity of FA-PEG-g-PAsp-CDDP, mPEG-g-PAsp-CDDP and CDDP in the FR over-expressing cell lines SPC-A-1 by CCK-8 test. In vivo, we compared their anti-tumor efficiency in tumor-bearing nude mice when the drugs were administered along or concurrent with radiation. The body weight change was also observed. The re- sults showed that in normal culture medium which contained over-dose folate, FA-PEG-g-PAsp-CDDP and mPEG-g-PAsp-CDDP had the same cytotoxicity, but it in folate-free culture medium, IC50 of FA-PEG-g-PAsp-CDDP was only about 1/3 of that in mPEG-g-PAsp-CDDP (p0.05). When administered along, the anti-tumor efficiency of FA-PEG-g-PAsp-CDDP and CDDP had no difference (p0.05), but both were higher than mPEG-g-PAsp-CDDP and blank control (p0.05). When concurrent with radiation, the anti-tumor efficiency of FA-PEG-g-PAsp-CDDP was higher than that of CDDP (p0.05), and both were higher than that of mPEG-g-PAsp-CDDP and radiation alone (p0.05). The body weight of nude mice was decreased by about 10% in CDDP group, but had no change in FA-PEG-g-PAsp-CDDP and mPEG-g-PAsp-CDDP groups. In conclusion, FA-PEG-g-PAsp-CDDP could inhibit the growth of tumors effectively. The folate receptor targeting group enhanced the anti-tumor efficiency of the micelles in FR over-expressing tumor. And FA-PEG-g-PAsp-CDDP has greater radio-sensitization effect and low toxicity than that of CDDP.
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