title: Cyclo(RGD)-Decorated Reduction-Responsive Nanogels Mediate Targeted Chemotherapy of Integrin Overexpressing Human Glioblastoma In Vivo.
abstract: Cyclo(Arg-Gly-Asp) peptide (cRGD) decorated disulfide (SS) containing poly(vinyl alcohol) nanogels (cRGD-SS-NGs) with an average diameter of 142 nm prepared by inverse nanoprecipitation, "click" reaction, and cRGD conjugation are developed for targeted treatment of integrin overexpressing human glioblastoma in vivo. Doxorubicin (DOX) release from cRGD-SS-NGs is highly inhibited under physiological conditions, while accelerated at endosomal pH and in response to cytoplasmic concentration of glutathione. Confocal microscopy shows that cRGD-SS-NGs facilitate the cellular uptake and intracellular DOX release in αvβ3integrin overexpressing human glioblastoma U87-MG cells. DOX-loaded cRGD-SS-NGs present much better killing activity toward U87-MG cells than that for nontargeted nanogels determined by MTT assay. The in vivo imaging and biodistribution studies reveal that DOX-loaded cRGD-SS-NGs have a much better tumor targetability toward human U87-MG glioblastoma xenograft in nude mice. Also the tumor growth is effectively inhibited by treatment with DOX-loaded cRGD-SS-NGs, while continuous tumor growth is observed for mice treated with nondecorated nanogels as well as free DOX. Furthermore, the treatment with DOX-loaded cRGD-SS-NGs has much fewer side effects, rendering these nanogels as a new platform for cancer chemotherapy in vivo.
authors.affiliation: Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 3, Berlin, 14195, Germany.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, Department of Polymer Science and Engineering, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, 215123, P. R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, Department of Polymer Science and Engineering, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, 215123, P. R. China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Zhong
authors.affiliation: Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 3, Berlin, 14195, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Haag
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D003952:Diagnostic Imaging; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D065546:Drug Liberation; D004705:Endocytosis / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D008819:Mice, Nude; D000080385:Nanogels; D009928:Organ Specificity; D010316:Particle Size; D010456:Peptides, Cyclic / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D011142:Polyvinyl Alcohol / Q000737:chemistry; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D016023:Integrins; D000080385:Nanogels; D010456:Peptides, Cyclic; C507169:cyclic arginine-glycine-aspartic acid peptide; C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; D004317:Doxorubicin; D011142:Polyvinyl Alcohol; D011094:Polyethyleneimine
keywords: PVA nanogels; cRGD-targeting; drug delivery; glioblastoma treatment; stimuli-responsive