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.