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- Title
Achievement of Release Mode under Combinational Stimuli by Acid and Reduction for Reduced Adverse Effect in Antitumor Efficacy.
- Authors
Song, Meifang; Xue, Yanan; Lin, Xiao; Xia, Xiaoyang; Chen, Lidi; Zhang, Liujie; Yu, Bo; Long, Sihui; Huang, Shiwen; Yu, Faquan
- Abstract
To reduce the adverse effect in antitumor therapy, a superparamagnetic doxorubicin (DOX)-loaded nanogel with the release mode under the combinational stimuli present in intracellular environments of solid tumors is presented. Dextran is first modified to involve both thiol groups and carboxyl groups. The dextran derivative is then covalently coupled with previously thiolated and aminated magnetic iron oxide nanoparticles through both the linkage of disulfide bond and electrostatic interaction. Upon the optimal conditions, a nanogel is fabricated via the dual cross-linking. The nanogel features the targeting release under combinational stimuli by acid and reduction environment with low release level in healthy tissues. In vitro release profiles reveal these release modes as expected. Cytotoxicity assay exhibits a much lower toxicity of the DOX-loaded nanogel to COS-7 cells than free DOX. Prussian blue staining and confocal laser scanning microscopy observation reveal the cellular uptake and subcellular release in nuclei of the nanogel. In vivo study exhibits that the nanogel presented 67.3% of inhibition rate of tumor growth and a healthy appearance. The present nanogel expresses high efficacy with low systemic adverse effect and is thus believed to offer a promising candidate for highly effective cancer therapy.
- Subjects
ANTINEOPLASTIC agents; SUPERPARAMAGNETIC materials; NANOGELS; ELECTROSTATIC interaction; MAGNETIC nanoparticles; IRON oxide nanoparticles
- Publication
Macromolecular Materials & Engineering, 2016, Vol 301, Issue 10, p1255
- ISSN
1438-7492
- Publication type
Article
- DOI
10.1002/mame.201600184