期刊
ACTA BIOMATERIALIA
卷 9, 期 1, 页码 4546-4557出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2012.08.017
关键词
Chitosan; Poly(ethylene glycol); pH-responsive nanogels; Remotely modulate; Drug delivery
资金
- American Diabetes Association [1-12-BS-243]
- Fundamental Research Funds for the Central Universities [2012121016]
- National Fund for Fostering Talents of Basic Science [J1030415]
- Xiamen University
A smart, soft and small nanoparticulate drug carrier that can efficiently transport therapeutics into tumor cells to control the intracellular drug concentration will enable major advancements in cancer therapy. To facilitate a remote modulation of the intracellular pH-regulated drug release, we have designed a new class of pH-responsive chitosan-based nanogels (<200 nm) by the physical interpenetration of chitosan chains into a nonlinear poly(ethylene glycol) (nonlinear PEG) chain network. The resultant PEG-chitosan nanogels not only respond to the changes in environmental pH over the physiologically important range of 5.0-7.4, but - more importantly - also enable us to remotely modulate the pH response by external cooling/heating. The nanogel, as well as the nanogel loaded with a model anticancer drug 5-fluorouracil (5-FU), is capable of varying its surface charge from nearly neutral to positive around tumor extracellular pH (similar to 6.0-6.2) to facilitate cell internalization. Subsequently, the significantly increased acidity in subcellular compartments (similar to 5.0) can trigger 5-FU release from the endocytosed drug carriers. While this nanogel serving as a drug carrier exhibits a reduced toxicity in combined chemo-thermo treatments, it has shown significantly enhanced therapeutic efficacy in combined chemo-cryo treatments of the model B16F10 melanoma cells, indicating its great potential for cancer therapy. (C) 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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