title: Glutathione-degradable drug-loaded nanogel effectively and securely suppresses hepatoma in mouse model.
abstract: The reduction-responsive polymeric nanocarriers have attracted considerable interest because of a significantly higher concentration of intracellular glutathione in comparison with that outside cells. The smart nanovehicles can selectively transport the antitumor drugs into cells to improve efficacies and decrease side effects. In this work, a facilely prepared glutathione-degradable nanogel was employed for targeting intracellular delivery of an antitumor drug (ie, doxorubicin [DOX]). DOX was loaded into nanogel through a sequential dispersion and dialysis approach with a drug loading efficiency of 56.8 wt%, and the laden nanogel (noted as NG/DOX) showed an appropriate hydrodynamic radius of 56.1±3.5 nm. NG/DOX exhibited enhanced or improved maximum tolerated dose on healthy Kunming mice and enhanced intratumoral accumulation and dose-dependent antitumor efficacy toward H22 hepatoma-xenografted mouse model compared with free drug. In addition, the upregulated antitumor efficacy of NG/DOX was further confirmed by the histopathological and immunohistochemical analyses. Furthermore, the excellent in vivo security of NG/DOX was confirmed by the detection of body weight, histopathology, and biochemical indices of corresponding organs and serum. With controllable large-scale preparation and fascinating in vitro and in vivo properties, the reduction-responsive nanogel exhibited a good prospect for clinical chemotherapy.
authors.affiliation: Department of Critical Care Medicine, The First Hospital of Jilin University, Changchun, People's Republic of China.
authors.forename: Xingang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Geriatrics, The First Hospital of Jilin University, Changchun, People's Republic of China.
authors.forename: Jianmeng
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Jilin University, Changchun, People's Republic of China.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Xu
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Jilin University, Changchun, People's Republic of China.
authors.forename: Jianxun
authors.initials: J
authors.lastname: Ding
authors.affiliation: Center for Biological Experiment, College of Basic Medicine, Jilin University, Changchun, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Shi
authors.affiliation: Center for Biological Experiment, College of Basic Medicine, Jilin University, Changchun, People's Republic of China.
authors.forename: Kexin
authors.initials: K
authors.lastname: Huang
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Jilin University, Changchun, People's Republic of China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Zhuang
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Jilin University, Changchun, People's Republic of China.
authors.forename: Xuesi
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology* / Q000627:therapeutic use; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005782:Gels; D005978:Glutathione / Q000378:metabolism*; D008113:Liver Neoplasms / Q000188:drug therapy*; D008297:Male; D051379:Mice; D050997:Nanomedicine / Q000379:methods*; D049329:Nanostructures / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D005782:Gels; D011108:Polymers; D004317:Doxorubicin; D005978:Glutathione
keywords: antitumor efficacy; chemotherapy; controlled release; nanogel; reduction-responsiveness; security