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Open AccessArticle

Discovery and in Vivo Evaluation of Novel RGD-Modified Lipid-Polymer Hybrid Nanoparticles for Targeted Drug Delivery

by 1,3,†, 2,†, 1,†, 3, 1,*, 1, 1, 4 and 1,*
1
State Key Laboratory of Biotherapy, Department of Pharmacy and Urology, West China Hospital, Sichuan University, Chengdu 610041, China
2
Department of Anesthesiology, Sichuan Academy of Medical Sciences & Sichuan Provincial Peopleʼs Hospital, Chengdu 610072, China
3
West China School of Pharmacy, Sichuan University, Chengdu 610041, China
4
State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2014, 15(10), 17565-17576; https://doi.org/10.3390/ijms151017565
Received: 25 July 2014 / Revised: 22 September 2014 / Accepted: 25 September 2014 / Published: 29 September 2014
(This article belongs to the Special Issue Bioactive Nanoparticles 2014)
In the current study, the lipid-shell and polymer-core hybrid nanoparticles (lpNPs) modified by Arg–Gly–Asp(RGD) peptide, loaded with curcumin (Cur), were developed by emulsification-solvent volatilization method. The RGD-modified hybrid nanoparticles (RGD–lpNPs) could overcome the poor water solubility of Cur to meet the requirement of intravenous administration and tumor active targeting. The obtained optimal RGD-lpNPs, composed of PLGA (poly(lactic-co-glycolic acid))–mPEG (methoxyl poly(ethylene- glycol)), RGD–polyethylene glycol (PEG)–cholesterol (Chol) copolymers and lipids, had good entrapment efficiency, submicron size and negatively neutral surface charge. The core-shell structure of RGD–lpNPs was verified by TEM. Cytotoxicity analysis demonstrated that the RGD–lpNPs encapsulated Cur retained potent anti-tumor effects. Flow cytometry analysis revealed the cellular uptake of Cur encapsulated in the RGD–lpNPs was increased for human umbilical vein endothelial cells (HUVEC). Furthermore, Cur loaded RGD–lpNPs were more effective in inhibiting tumor growth in a subcutaneous B16 melanoma tumor model. The results of immunofluorescent and immunohistochemical studies by Cur loaded RGD–lpNPs therapies indicated that more apoptotic cells, fewer microvessels, and fewer proliferation-positive cells were observed. In conclusion, RGD–lpNPs encapsulating Cur were developed with enhanced anti-tumor activity in melanoma, and Cur loaded RGD–lpNPs represent an excellent tumor targeted formulation of Cur which might be an attractive candidate for cancer therapy. View Full-Text
Keywords: curcumin; lipid-shell and polymer-core hybrid nanoparticle (lpNP); PLGA; RGD curcumin; lipid-shell and polymer-core hybrid nanoparticle (lpNP); PLGA; RGD
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MDPI and ACS Style

Zhao, Y.; Lin, D.; Wu, F.; Guo, L.; He, G.; Ouyang, L.; Song, X.; Huang, W.; Li, X. Discovery and in Vivo Evaluation of Novel RGD-Modified Lipid-Polymer Hybrid Nanoparticles for Targeted Drug Delivery. Int. J. Mol. Sci. 2014, 15, 17565-17576. https://doi.org/10.3390/ijms151017565

AMA Style

Zhao Y, Lin D, Wu F, Guo L, He G, Ouyang L, Song X, Huang W, Li X. Discovery and in Vivo Evaluation of Novel RGD-Modified Lipid-Polymer Hybrid Nanoparticles for Targeted Drug Delivery. International Journal of Molecular Sciences. 2014; 15(10):17565-17576. https://doi.org/10.3390/ijms151017565

Chicago/Turabian Style

Zhao, Yinbo; Lin, Dayong; Wu, Fengbo; Guo, Li; He, Gu; Ouyang, Liang; Song, Xiangrong; Huang, Wei; Li, Xiang. 2014. "Discovery and in Vivo Evaluation of Novel RGD-Modified Lipid-Polymer Hybrid Nanoparticles for Targeted Drug Delivery" Int. J. Mol. Sci. 15, no. 10: 17565-17576. https://doi.org/10.3390/ijms151017565

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