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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 1H-NMR spectra of F127-COOH, F127-NHS and c(RGDyK)-F127.Notes: (A) 1H-NMR spectra of F127-COOH; (B) F127-NHS; (C) c(RGDyK)-F127.Abbreviations:1H-NMR, 1H-nuclear magnetic resonance spectroscopy; NHS, N-hydroxysuccinimide; c(RGDyK), cyclic RGD peptide; RGD, arginine-glycine-aspartic acid; DMSO, dimethyl sulfoxide.
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f2-ijn-10-4863: The 1H-NMR spectra of F127-COOH, F127-NHS and c(RGDyK)-F127.Notes: (A) 1H-NMR spectra of F127-COOH; (B) F127-NHS; (C) c(RGDyK)-F127.Abbreviations:1H-NMR, 1H-nuclear magnetic resonance spectroscopy; NHS, N-hydroxysuccinimide; c(RGDyK), cyclic RGD peptide; RGD, arginine-glycine-aspartic acid; DMSO, dimethyl sulfoxide.

Mentions: As shown in 1H-NMR spectrum, the solvent peak of CDCl3 was found at 7.25 ppm (Figure 2A and C) and of DMSO-d6 was found at 2.48 ppm (Figure 2B). The peaks at 1.14 ppm and 3.40–3.60 ppm were attributed to −CH3 of PPO and −CH2CHO of PPO and PEO in F127, respectively. As shown in Figure 2B, F127-COOH copolymer was activated by the reaction with NHS. The characteristic peak at 2.52 ppm was assigned to the protons of the NHS unit, indicating the addition of NHS to the PEO terminus. The excessive c(RGDyK) was removed by dialysis against deionized water. There was a characteristic peak of the –CH2–CH2– group in c(RGDyK) at 2.17 ppm (Figure 2C). The yield of F127-COOH, F127-NHS, and c(RGDyK)-F127 was 75.9%, 83.4%, and 89.2%, respectively. The conjugation percentage of c(RGDyK) to Pluronic F127 was 91.44% on a molar ratio basis.


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 1H-NMR spectra of F127-COOH, F127-NHS and c(RGDyK)-F127.Notes: (A) 1H-NMR spectra of F127-COOH; (B) F127-NHS; (C) c(RGDyK)-F127.Abbreviations:1H-NMR, 1H-nuclear magnetic resonance spectroscopy; NHS, N-hydroxysuccinimide; c(RGDyK), cyclic RGD peptide; RGD, arginine-glycine-aspartic acid; DMSO, dimethyl sulfoxide.
© Copyright Policy
Related In: Results  -  Collection

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

f2-ijn-10-4863: The 1H-NMR spectra of F127-COOH, F127-NHS and c(RGDyK)-F127.Notes: (A) 1H-NMR spectra of F127-COOH; (B) F127-NHS; (C) c(RGDyK)-F127.Abbreviations:1H-NMR, 1H-nuclear magnetic resonance spectroscopy; NHS, N-hydroxysuccinimide; c(RGDyK), cyclic RGD peptide; RGD, arginine-glycine-aspartic acid; DMSO, dimethyl sulfoxide.
Mentions: As shown in 1H-NMR spectrum, the solvent peak of CDCl3 was found at 7.25 ppm (Figure 2A and C) and of DMSO-d6 was found at 2.48 ppm (Figure 2B). The peaks at 1.14 ppm and 3.40–3.60 ppm were attributed to −CH3 of PPO and −CH2CHO of PPO and PEO in F127, respectively. As shown in Figure 2B, F127-COOH copolymer was activated by the reaction with NHS. The characteristic peak at 2.52 ppm was assigned to the protons of the NHS unit, indicating the addition of NHS to the PEO terminus. The excessive c(RGDyK) was removed by dialysis against deionized water. There was a characteristic peak of the –CH2–CH2– group in c(RGDyK) at 2.17 ppm (Figure 2C). The yield of F127-COOH, F127-NHS, and c(RGDyK)-F127 was 75.9%, 83.4%, and 89.2%, respectively. The conjugation percentage of c(RGDyK) to Pluronic F127 was 91.44% on a molar ratio basis.

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