Fabrication of poly(γ-glutamic acid)-based biopolymer as the targeted drug delivery system with enhanced cytotoxicity to APN/CD13 over-expressed cells

Poly(γ-glutamic acid)-based targeted drug delivery system (PAMCN) targeting transmembrane metalloprotease aminopeptidase-N (APN/CD13) was fabricated and evaluated for the enhancement of targeting efficiency and cytotoxicity. The cisplatin (CDDP) loading content of PAMCN was about 36 ± 5% and PAMCN showed a sustainable release profile with a half-maximal release time (t1/2) of 23 h. The average size of PAMCN was 132 ± 18 nm determined by light scattering (LS) and 158 ± 67 nm by atomic force microscopy (AFM). Flow cytometry and fluorescence microscope analysis showed that the drug carrier (PAMN) could specifically bind to human umbilical vein endothelial cells (HUVEC). PAMCN enhanced the efficacy of CDDP to HUVEC cells with the half maximal inhibitory concentration (IC50) value decreased to 90.83 ± 33.00 μg/ml comparing with free CDDP treatment and showed less tube formation amounts (p < 0.01) than free CDDP in matrigel angiogenesis inhibition assay in vitro. In vivo toxicity experiment indicated that the survival rate of KM mice in PAMCN group was 100% and PAMCN reduced the hepatic and renal toxicity significantly compared to free CDDP group. Therefore, this novel drug delivery system presents a promising potential for antiangiogenic chemotherapy.