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A micellar cisplatin prodrug simultaneously eliminates both cancer cells and cancer stem cells in lung cancer

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Abstract

Platinum-based chemotherapy as first-line treatment for lung cancers encounters insufficient selectivity, severe side effects and drug resistance in clinics. In this study, we developed an amphiphilic prodrug of cisplatin-poly(ethylene glycol)-block-polycaprolactone and demonstrated that the prodrug formed micellar nanoparticles, NPPt(IV), with an average diameter of ∼100 nm. NPPt(IV) released platinum in response to the intracellular acidic and reductive environment, and in turn induced significant anti-proliferative activity in lung cancer cells. More importantly, NPPt(IV) exhibited a prominent inhibitory effect on CD133+ lung cancer stem cells (CSCs) and suppressed tumor growth in vivo. Unlike cisplatin treatment which eventually enriches CSCs, NPPt(IV) treatment prevents the accumulation of CD133+ lung CSCs in tumors. Therefore, NPPt(IV) simutaneously targeting CSCs and non-CSCs might represent a superior strategy to improve conventional anticancer therapy directed predominantly to tumor bulk populations.

Graphical abstract: A micellar cisplatin prodrug simultaneously eliminates both cancer cells and cancer stem cells in lung cancer

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Publication details

The article was received on 30 Mar 2017, accepted on 15 May 2017 and first published on 18 May 2017


Article type: Paper
DOI: 10.1039/C7BM00278E
Citation: Biomater. Sci., 2017, Advance Article
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    A micellar cisplatin prodrug simultaneously eliminates both cancer cells and cancer stem cells in lung cancer

    Y. Zhu, C. Sun, S. Shen, M. I. U. Khan, Y. Zhao, Y. Liu, Y. Wang and J. Wang, Biomater. Sci., 2017, Advance Article , DOI: 10.1039/C7BM00278E

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