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Dual-functional c(RGDyK)-decorated Pluronic micelles designed for antiangiogenesis and the treatment of drug-resistant tumor.

Chen Y, Zhang W, Huang Y, Gao F, Fang X - Int J Nanomedicine (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics, School of Pharmacy, East China University of Science and Technology, Fudan University, Shanghai, People's Republic of China ; Key Laboratory of Smart Drug Delivery, Ministry of Education and PLA, School of Pharmacy, Fudan University, Shanghai, People's Republic of China.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

The schematic illustration of the c(RGDyK)-F127 synthesis and the preparation of c(RGDyK)-decorated Pluronic micelles loaded with DOX and PTX.Notes: (A) Synthesis of c(RGDyK)-decorated Pluronic F127; (B) Schematic representation of the fabrication of c(RGDyK)-decorated Pluronic micelles loaded with DOX and PTX.Abbreviations: c(RGDyK), cyclic RGD peptide; RGD, arginine-glycine-aspartic acid; DOX, doxorubicin; PTX, paclitaxel; RT, room temperature; DCC, dicyclohexyl-carbodiimide; NHS, N-hydroxysuccinimide.
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f1-ijn-10-4863: The schematic illustration of the c(RGDyK)-F127 synthesis and the preparation of c(RGDyK)-decorated Pluronic micelles loaded with DOX and PTX.Notes: (A) Synthesis of c(RGDyK)-decorated Pluronic F127; (B) Schematic representation of the fabrication of c(RGDyK)-decorated Pluronic micelles loaded with DOX and PTX.Abbreviations: c(RGDyK), cyclic RGD peptide; RGD, arginine-glycine-aspartic acid; DOX, doxorubicin; PTX, paclitaxel; RT, room temperature; DCC, dicyclohexyl-carbodiimide; NHS, N-hydroxysuccinimide.

Mentions: The scheme for the synthesis of c(RGDyK)-F127 is shown in Figure 1A. Briefly, F127-COOH (0.67 g, 0.053 mM), N,N′-dicyclohexyl carbodiimide (0.0219 g, 0.106 mM), NHS (0.0122 g, 0.106 mM), and 5 mL of dichloromethane were added to a round-bottom flask equipped with a magnetic stirring bar, attached to a nitrogen line and a bubbler. The reaction was maintained for 24 hours at room temperature. The reaction mixture was then filtered, concentrated under reduced pressure, and precipitated in cold diethyl ether and dried under vacuum at room temperature to obtain F127-NHS.


Dual-functional c(RGDyK)-decorated Pluronic micelles designed for antiangiogenesis and the treatment of drug-resistant tumor.

Chen Y, Zhang W, Huang Y, Gao F, Fang X - Int J Nanomedicine (2015)

The schematic illustration of the c(RGDyK)-F127 synthesis and the preparation of c(RGDyK)-decorated Pluronic micelles loaded with DOX and PTX.Notes: (A) Synthesis of c(RGDyK)-decorated Pluronic F127; (B) Schematic representation of the fabrication of c(RGDyK)-decorated Pluronic micelles loaded with DOX and PTX.Abbreviations: c(RGDyK), cyclic RGD peptide; RGD, arginine-glycine-aspartic acid; DOX, doxorubicin; PTX, paclitaxel; RT, room temperature; DCC, dicyclohexyl-carbodiimide; NHS, N-hydroxysuccinimide.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4525800&req=5

f1-ijn-10-4863: The schematic illustration of the c(RGDyK)-F127 synthesis and the preparation of c(RGDyK)-decorated Pluronic micelles loaded with DOX and PTX.Notes: (A) Synthesis of c(RGDyK)-decorated Pluronic F127; (B) Schematic representation of the fabrication of c(RGDyK)-decorated Pluronic micelles loaded with DOX and PTX.Abbreviations: c(RGDyK), cyclic RGD peptide; RGD, arginine-glycine-aspartic acid; DOX, doxorubicin; PTX, paclitaxel; RT, room temperature; DCC, dicyclohexyl-carbodiimide; NHS, N-hydroxysuccinimide.
Mentions: The scheme for the synthesis of c(RGDyK)-F127 is shown in Figure 1A. Briefly, F127-COOH (0.67 g, 0.053 mM), N,N′-dicyclohexyl carbodiimide (0.0219 g, 0.106 mM), NHS (0.0122 g, 0.106 mM), and 5 mL of dichloromethane were added to a round-bottom flask equipped with a magnetic stirring bar, attached to a nitrogen line and a bubbler. The reaction was maintained for 24 hours at room temperature. The reaction mixture was then filtered, concentrated under reduced pressure, and precipitated in cold diethyl ether and dried under vacuum at room temperature to obtain F127-NHS.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics, School of Pharmacy, East China University of Science and Technology, Fudan University, Shanghai, People's Republic of China ; Key Laboratory of Smart Drug Delivery, Ministry of Education and PLA, School of Pharmacy, Fudan University, Shanghai, People's Republic of China.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus