title: Discovery and in vivo evaluation of novel RGD-modified lipid-polymer hybrid nanoparticles for targeted drug delivery.
abstract: 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.
authors.affiliation: State Key Laboratory of Biotherapy, Department of Pharmacy and Urology, West China Hospital, Sichuan University, Chengdu 610041, China. sklb_zhaoyinbo@126.com.
authors.forename: Yinbo
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu 610072, China. dyl_spph@126.com.
authors.forename: Dayong
authors.initials: D
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Biotherapy, Department of Pharmacy and Urology, West China Hospital, Sichuan University, Chengdu 610041, China. wufengbo_@163.com.
authors.forename: Fengbo
authors.initials: F
authors.lastname: Wu
authors.affiliation: West China School of Pharmacy, Sichuan University, Chengdu 610041, China. guoli@scu.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Biotherapy, Department of Pharmacy and Urology, West China Hospital, Sichuan University, Chengdu 610041, China. hegu@scu.edu.cn.
authors.forename: Gu
authors.initials: G
authors.lastname: He
authors.affiliation: State Key Laboratory of Biotherapy, Department of Pharmacy and Urology, West China Hospital, Sichuan University, Chengdu 610041, China. ouyangliang@scu.edu.cn.
authors.forename: Liang
authors.initials: L
authors.lastname: Ouyang
authors.affiliation: State Key Laboratory of Biotherapy, Department of Pharmacy and Urology, West China Hospital, Sichuan University, Chengdu 610041, China. xiangrong_11@126.com.
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Song
authors.affiliation: State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China. huangwei@cdutcm.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Biotherapy, Department of Pharmacy and Urology, West China Hospital, Sichuan University, Chengdu 610041, China. xiangli.87@163.com.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000031:analogs & derivatives / Q000737:chemistry; D003474:Curcumin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry*; D004353:Drug Evaluation, Preclinical; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry; D008055:Lipids / Q000737:chemistry*; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry*; D011091:Polyesters; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D014184:Transplantation, Homologous
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008055:Lipids; D009842:Oligopeptides; D011091:Polyesters; D011108:Polymers; C118255:polyethylene glycol-cholesterol; D019344:Lactic Acid; D011092:Polyethylene Glycols; C033616:poly(lactide); C047981:arginyl-glycyl-aspartic acid; D002784:Cholesterol; D003474:Curcumin