title: Degradable and biocompatible nanoparticles decorated with cyclic RGD peptide for efficient drug delivery to hepatoma cells in vitro.
abstract: Amphiphilic derivatives of poly(benzyl malate) were synthesized and characterized with the aim of being used as degradable and biocompatible building blocks for the design of functional nanoparticles (NPs). An anti-cancer model drug, doxorubicin, has been successfully encapsulated into the prepared NPs and its release profile has been evaluated in water and in culture medium. NPs bearing biotin molecules were prepared either for site-specific drug delivery via the targeting of biotin receptors overexpressed on the surface of several cancer cells, or for grafting biotinylated cyclic RGD peptide onto their surface using the strong and highly specific interactions between biotin and the streptavidin protein. We have shown that this binding did not affect dramatically the physico-chemical properties of the corresponding NPs. Cyclic RGD grafted fluorescent NPs were more efficiently uptaken by the HepaRG hepatoma cells than biotinylated fluorescent NPs. Furthermore, the targeting of HepaRG hepatoma cells with NPs bearing cyclic RGD was very efficient and much weaker for HeLa and HT29 cell lines confirming that cyclic RGD is a suitable targeting agent for liver cells. Our results also provide a new mean for rapid screening of short hepatotropic peptides in order to design NPs showing specific liver targeting properties.
authors.affiliation: Inserm UMR S-991, Foie, Métabolismes et Cancer, Université de Rennes 1, Fédération de Recherche de Rennes Biosit, CHU Rennes, 35033 Rennes, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Loyer
authors.forename: Wahib
authors.initials: W
authors.lastname: Bedhouche
authors.forename: Zhi Wei
authors.initials: ZW
authors.lastname: Huang
authors.forename: Sandrine
authors.initials: S
authors.lastname: Cammas-Marion
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000737:chemistry*; D001710:Biotin / Q000737:chemistry; D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000737:chemistry*; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000737:chemistry*; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D010456:Peptides, Cyclic; D011091:Polyesters; C507169:cyclic arginine-glycine-aspartic acid peptide; C586825:poly(benzyl malate); D011092:Polyethylene Glycols; D001710:Biotin; D004317:Doxorubicin
keywords: Anti-cancer drug encapsulation; Biotinylated nanoparticles; Cyclic RGD peptide; Degradable poly(benzyl malate) derivatives; HepaRG hepatoma cells; Site-specific targeting