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Issue 8, 2017
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Phosphatase-triggered cell-selective release of a Pt(iv)-backboned prodrug-like polymer for an improved therapeutic index

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Abstract

We describe here the synthesis and cell-selective delivery of a cationic Pt(IV)-backboned prodrug-like polymer P(DSP-DAEP). P(DSP-DAEP) features excellent aqueous solubility, unusually high (44.5%) drug loading, can be rapidly reduced to release the active cisplatin, and is more potent than its small molecular Pt(IV) precursor DSP. P(DSP-DAEP) can be formulated with an oppositely charged methoxyl poly(ethylene glycol)-block-poly(L-phosphotyrosine) (mPEG-b-PpY) to afford a polyion micelle (Pt-PIC) by taking advantage of polyelectrolyte coacervation. Preliminary in vitro cellular uptake and cytotoxicity assays indicate that Pt-PIC exhibits receptor (surface alkaline phosphatase)-dependent uptake and cytotoxicity. Overall, our results suggest a new approach to the improved therapeutic index of platinum-based anticancer drugs via cell-selective delivery.

Graphical abstract: Phosphatase-triggered cell-selective release of a Pt(iv)-backboned prodrug-like polymer for an improved therapeutic index

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Supplementary files

Article information


Submitted
22 Dec 2016
Accepted
02 Feb 2017
First published
09 Feb 2017

Biomater. Sci., 2017,5, 1558-1566
Article type
Paper

Phosphatase-triggered cell-selective release of a Pt(IV)-backboned prodrug-like polymer for an improved therapeutic index

S. Li, Y. Hou, Y. Hu, J. Yu, W. Wei and H. Lu, Biomater. Sci., 2017, 5, 1558
DOI: 10.1039/C6BM00935B

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