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Acid- and reduction-sensitive micelles for improving the drug delivery efficacy for pancreatic cancer therapy

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Abstract

One of the major challenges in anticancer therapy is the poor penetration of anticancer drugs into tumors, especially in solid tumors, resulting in decreased therapeutic efficacy in vivo. To solve some of these problems, in this study, a dual-responsive polymeric micellar system has been developed. This system exhibits an ultrasensitive response to the change of pH value from the extracellular environment to the intracellular environment, resulting in micellar swelling in cancer cells via the proton sponge effect. Moreover, once the swelled micelles escape from the lysosomes in cancer cells, the disulfide linkages are ruptured by GSH in the cytoplasm, leading to the rapid release of the encapsulated drugs into the cellular nuclei. The antitumor activity in pancreatic tumor-bearing mice reveals that this dual-responsive drug delivery system possesses a long blood circulation time and can significantly promote cell internalization and intracellular drug release, achieving a high anticancer efficacy with fewer side effects for normal tissues.

Graphical abstract: Acid- and reduction-sensitive micelles for improving the drug delivery efficacy for pancreatic cancer therapy

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Publication details

The article was received on 14 Nov 2017, accepted on 23 Feb 2018 and first published on 09 Mar 2018


Article type: Paper
DOI: 10.1039/C7BM01051F
Citation: Biomater. Sci., 2018, Advance Article
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    Acid- and reduction-sensitive micelles for improving the drug delivery efficacy for pancreatic cancer therapy

    P. Wang, J. Wang, H. Tan, S. Weng, L. Cheng, Z. Zhou and S. Wen, Biomater. Sci., 2018, Advance Article , DOI: 10.1039/C7BM01051F

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