Dual-functional drug delivery system was developed by decorating c(RGDyK) (
cyclic RGD [
arginine-glycine-aspartic acid]
peptide) with
Pluronic polymeric
micelles (c[RGDyK]-FP-DP) to overcome the drawbacks of low transport of chemotherapeutics across the blood-
tumor barrier and poor multidrug-resistant (MDR)
tumor therapy. c(RGDyK) that can bind to the
integrin protein richly expressed at the site of
tumor vascular endothelial cells and
tumor cells with high affinity and specificity was conjugated to the
N-hydroxysuccinimide-activated PEO terminus of the
Pluronic F127 block copolymer. In this study, decreased
tumor angiogenic and increased apoptotic activity in MDR
cancer cells were observed after the treatment with c(RGDyK)-FP-DP. c(RGDyK)-FP-DP was fully characterized in terms of morphology, particle size, zeta potential, and drug release. Importantly, in vitro antiangiogenesis results demonstrated that c(RGDyK)-FP-DP had a significant inhibition effect on the tubular formation of human umbilical vein endothelial cells and promoted cellular apoptotic activity in MDR KBv cells. In addition, the growth inhibition efficacy of KBv
tumor spheroids after crossing the blood-
tumor barrier was obviously increased by c(RGDyK)-FP-DP compared to other control groups. Results suggested that c(RGDyK)-decorated
Pluronic polymeric
micelles can take pharmacological action on both human umbilical vein endothelial cells and KBv MDR
cancer cells, resulting in a dual-functional anticancer effect similar to that observed in our in vitro cellular studies.