title: Intracellularly Swollen Polypeptide Nanogel Assists Hepatoma Chemotherapy.
abstract: Nowadays, chemotherapy is one of the principal modes of treatment for tumor patients. However, the traditional formulations of small molecule drugs show short circulation time, low tumor selectivity, and high toxicity to normal tissues. To address these problems, a facilely prepared, and pH and reduction dual-responsive polypeptide nanogel was prepared for selectively intracellular delivery of chemotherapy drug. As a model drug, doxorubicin (DOX) was loaded into the nanogel through a sequential dispersion and dialysis technique, resulting in a high drug loading efficiency (DLE) of 96.7 wt.%. The loading nanogel, defined as NG/DOX, exhibited a uniform spherical morphology with a mean hydrodynamic radius of 58.8 nm, pH and reduction dual-triggered DOX release, efficient cell uptake, and cell proliferation inhibitionin vitro. Moreover, NG/DOX exhibited improved antitumor efficacy toward H22 hepatoma-bearing BALB/c mouse model compared with free DOX·HCl. Histopathological and immunohistochemical analyses were implemented to further confirm the tumor suppression activity of NG/DOX. Furthermore, the variations of body weight, histopathological morphology, bone marrow cell micronucleus rate, and white blood cell count verified that NG/DOX showed excellent safetyin vivo. With these excellent propertiesin vitroandin vivo, the pH and reduction dual-responsive polypeptide nanogel exhibits great potential for on-demand intracellular delivery of antitumor drug, and holds good prospect for future clinical application.
authors.affiliation: Center for Biological Experiment, College of Basic Medicine, Jilin University, Changchun 130021, 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 130021, 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, Changchun 130022, People's Republic of China.
authors.forename: Jianxun
authors.initials: J
authors.lastname: Ding
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, People's Republic of China.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Xu
authors.affiliation: Center for Biological Experiment, College of Basic Medicine, Jilin University, Changchun 130021, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Center for Biological Experiment, College of Basic Medicine, Jilin University, Changchun 130021, People's Republic of China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104-6321, United States of America.
authors.forename: Lesan
authors.initials: L
authors.lastname: Yan
authors.affiliation: Key Laboratory of Polymer Ecomaterials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, People's Republic of China.
authors.forename: Xuesi
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy*; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000008:administration & dosage*; D004358:Drug Therapy / Q000379:methods*; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008807:Mice, Inbred BALB C; D000080385:Nanogels; D010084:Oxidation-Reduction; D010455:Peptides / Q000008:administration & dosage*; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011094:Polyethyleneimine / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D000080385:Nanogels; D010455:Peptides; C413692:polyethylene glycol polyethyleneimine nanogel; D011092:Polyethylene Glycols; D004317:Doxorubicin; D011094:Polyethyleneimine
keywords: Hepatoma Chemotherapy.; Intracellular Drug Delivery; Polypeptide Nanogel; Stimuli-Responsiveness