Redox-Responsive Nanogel with Intracellular Reconstruction and Programmable Drug Release for Targeted Tumor Therapy.

Abstract

A tumor-selective drug delivery nanogel with redox-responsive size swelling and co-instantaneous drug release is developed. The nanogel is formed by poly(ethylene glycol) diglycidyl ether and cystamine double crosslinked hyaluronic acid (HA). The disulfide bond in cystamine (Cys) is in charge of the responsiveness, while the compact polymer network turns the nanogel a capsule for effective drug loading. The tumor targeting is achieved by the known HA-receptor mediated endocytosis. The responsive swelling of this nanogel and co-instantaneous drug releases happen with the cleavage of the disulfide bond following tumor targeting and cell endocytosis, which is triggered by massive glutathione (GSH) in the cytoplasm of tumor cells. The highly selective nanogel uptake by tumor cells is directly demonstrated by fluorescence microscopy and flow cytometry. The dynamic light scattering and fluorescent spectrum reveal the GSH-triggered size change and simultaneous drug release, which results in higher tumor cytotoxicity and over fourfold efficacy against tumor cells compared with normal cells. These results indicate that these HA-PEG-Cys-DOX nanogels, with performance of selective drug delivery, intracellular reconstruction, and responsive drug release, are promising platforms for better therapeutic effects in cancer treatment.

• Authors: Yu Tian, Ran Tian, Li Chen, Ronghua Jin, Yiming Feng, Yongkang Bai, Xin Chen
• Journal: Macromolecular rapid communications (Macromol Rapid Commun) Vol. 40 Issue 8 Pg. e1800824 (Apr 2019) ISSN: 1521-3927 [Electronic] Germany
• PMID: 30779386 (Publication Type: Journal Article)
• Copyright: © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Antibiotics, Antineoplastic
• Nanogels
• polyethylene glycol polyethyleneimine nanogel
• Polyethylene Glycols
• Doxorubicin
• Polyethyleneimine
• Hyaluronic Acid
• Cystamine

Topics

• Antibiotics, Antineoplastic (administration & dosage, chemistry, therapeutic use)
• Cell Line
• Cell Proliferation (drug effects)
• Cystamine (chemistry)
• Doxorubicin (administration & dosage, therapeutic use)
• Drug Delivery Systems (methods)
• Drug Liberation
• Drug Screening Assays, Antitumor
• Humans
• Hyaluronic Acid (chemistry)
• Nanogels
• Neoplasms (drug therapy, pathology)
• Oxidation-Reduction
• Polyethylene Glycols (chemistry)
• Polyethyleneimine (chemistry)