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.

Polypeptide Nanogels With Different Functional Cores Promote Chemotherapy of Lung Carcinoma

“…The disulfide bond of the LC segment endowed the nanogels with reduction-responsiveness (Huang et al, 2015; Shi et al, 2017). These DOX-loaded nanogels were prepared through a modified nanoprecipitation method by adding DOX aqueous solution to dimethylformamide (DMF) solution containing NGP or NGG nanogel (Scheme 1) (Ding et al, 2013a; Huang et al, 2015; Liu et al, 2015; Shi et al, 2017). The drug loading content (DLCs) and drug loading efficiency (DLEs) of NGP/DOX and NGG/DOX were calculated to be 9.8, 54.7 and 15.2, 91.5 wt.%, respectively.…”

Tumor Microenvironment–Responsive Polypeptide Nanogels for Controlled Antitumor Drug Delivery

“…Liu et al ( Liu et al, 2015 ) prepared a reduction-reactive nanogel methoxy poly (ethylene glycol)-poly ( l -phenylalanine-co- l -cystine) (mPEG-P (LP-co-LC)) with a medium drug loading of 10.2 wt% and a diameter of less than 110 nm. DOX was used as a model antitumor drug loaded onto the nanogels to treat liver cancer in rodent models.…”

Polymer Nanoformulation of Sorafenib and All-Trans Retinoic Acid for Synergistic Inhibition of Thyroid Cancer

“…Nanocarriers are characterized by good biocompatibility, high drug loading efficiency, prolonged circulation time in vivo, increased aggregation in tumor tissues, surface modification to actively target specific tissues and cells, stimuli-sensitive behavior for controlled drug release, and simultaneous delivery of different drugs for combination therapy (Feng et al, 2017;Xu et al, 2017;Guo et al, 2018;Zhang et al, 2018a;Feng et al, 2019;Wang et al, 2019). In recent years, a variety of multifunctional nanomaterials have been developed for co-delivery of multiple drugs, such as polymer nanoparticles (Zhao et al, 2016), micelles (Wang et al, 2018;Yang et al, 2019), liposomes (Yao et al, 2015), inorganic nanoparticles (Zhang et al, 2016b), and nanogels (Liu et al, 2015;Zhang et al, 2018b). These delivery systems can deliver drugs to tumor tissues more effectively and safely, thus improving the therapeutic effect.…”