title: Carboplatin-Complexed and cRGD-Conjugated Unimolecular Nanoparticles for Targeted Ovarian Cancer Therapy.
abstract: Platinum-based chemotherapy has been widely used to treat cancers including ovarian cancer; however, it suffers from dose-limiting toxicity. Judiciously designed drug nanocarriers can enhance the anticancer efficacy of platinum-based chemotherapy while reducing its systemic toxicity. Herein the authors report a stable and water-soluble unimolecular nanoparticle constructed from a hydrophilic multi-arm star block copolymer poly(amidoamine)-b-poly(aspartic acid)-b-poly(ethylene glycol) (PAMAM-PAsp-PEG) conjugated with both cRGD (cyclo(Arg-Gly-Asp-D-Phe-Cys) peptide and cyanine5 (Cy5) fluorescent dye as a platinum-based drug nanocarrier for targeted ovarian cancer therapy. Carboplatin is complexed to the poly(aspartic acid) inner shell via pH-responsive ion-dipole interactions between carboplatin and the carboxylate groups of poly(aspartic acid). Based on flow cytometry and confocal laser scanning microscopy analyses, cRGD-conjugated unimolecular nanoparticles exhibit much higher cellular uptake by ovarian cancer cells overexpressing αvβ3integrin than nontargeted (i.e., cRGD-lacking) ones. Carboplatin-complexed cRGD-conjugated nanoparticles also exhibit higher cytotoxicity than nontargeted nanoparticles as well as free carboplatin, while empty unimolecular nanoparticles show no cytotoxicity. These results indicate that stable unimolecular nanoparticles made of individual hydrophilic multi-arm star block copolymer molecules conjugate with tumor-targeting ligands and dyes (i.e., PAMAM-PAsp-PEG-cRGD/Cy5) are promising nanocarriers for platinum-based anticancer drugs for targeted cancer therapy.
authors.affiliation: Department of Materials Science and Engineering and Wisconsin Institutes for Discovery, Madison, WI, 53715, USA.
authors.forename: Yuyuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, 53706, USA.
authors.forename: Liwei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Materials Science and Engineering and Wisconsin Institutes for Discovery, Madison, WI, 53715, USA.
authors.forename: Guojun
authors.initials: G
authors.lastname: Chen
authors.affiliation: Department of Materials Science and Engineering and Wisconsin Institutes for Discovery, Madison, WI, 53715, USA.|Department of Biomedical Engineering, University of Wisconsin-Madison, Madison, WI, 53706, USA.
authors.forename: Shaoqin
authors.initials: S
authors.lastname: Gong
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use*; D016190:Carboplatin / Q000737:chemistry / Q000627:therapeutic use*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D018613:Microscopy, Confocal; D053758:Nanoparticles; D009842:Oligopeptides / Q000737:chemistry*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011108:Polymers / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D009842:Oligopeptides; D011108:Polymers; C047981:arginyl-glycyl-aspartic acid; D016190:Carboplatin
keywords: cancer chemotherapy; platinum-based drugs; targeted drug delivery; unimolecular nanoparticle