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Issue 13, 2017
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Tunable dynamic fluorinated poly(orthoester)-based drug carriers for greatly enhanced chemotherapeutic efficacy

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Abstract

To promote chemotherapeutic efficacy, a dynamic drug delivery system was prepared, which remained stealthy and stable in blood vessels, improved drug penetration and retention in response to extracellular stimuli, enhanced membrane permeability through unique functional groups, and then achieved rapid drug release to improve toxicity to tumor cells in response to intracellular stimuli. Herein, fluorinated poly(orthoester)-based nanospheres-doxorubicin (POEAd-g-F-DOX), which were constructed by a facile method, can respond to both extracellular and intracellular pH in a controlled manner and can easily pass through cell membranes by fluorination, are reported for the first time as drug carriers; they demonstrate (i) stability at pH 7.4; (ii) response to tumoral extracellular pH following dynamic size changes; (iii) crossing of cell membranes; and (iv) sensitivity to tumoral intracellular pH following dissolution or further swelling for rapid drug release. POEAd-g-F-DOX exhibits greatly enhanced chemotherapeutic efficacy because of its tunable dynamic changes and fluorination, resulting in improved cellular uptake and greater toxic effects on tumor cells than free DOX, stronger penetration and unprecedentedly rapid complete destruction of 3-D tumor spheroids in vitro, and significant tumor accumulation and inhibition with decreasing side effects in normal organs in vivo.

Graphical abstract: Tunable dynamic fluorinated poly(orthoester)-based drug carriers for greatly enhanced chemotherapeutic efficacy

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Publication details

The article was received on 21 Dec 2016, accepted on 03 Mar 2017 and first published on 06 Mar 2017


Article type: Paper
DOI: 10.1039/C6PY02204A
Citation: Polym. Chem., 2017,8, 2063-2073
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    Tunable dynamic fluorinated poly(orthoester)-based drug carriers for greatly enhanced chemotherapeutic efficacy

    G. Yan, J. Wang, P. Zhang, L. Hu, X. Wang, G. Yang, S. Fu, X. Cheng and R. Tang, Polym. Chem., 2017, 8, 2063
    DOI: 10.1039/C6PY02204A

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