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美國布魯克海文儀器公司>技術(shù)文章>Phosphatase-triggered cell-selective release of a Pt(IV)-backboned prodrug-like polymer for an impro

技術(shù)文章

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

閱讀:284          發(fā)布時間:2017-12-22
 作者 Shao-Lu Li,a  Yingqin Hou,a  Yali Hu,a  Jin Yu,a  Wei Wei*b  and  Hua Lu*a

aBeijing National Laboratory for Molecular Sciences, Center for Soft Matter Science and Engineering, Key Laboratory of Polymer Chemistry and Physics of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, People's Republic of China

bState Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing, 10090, People's Republic of China

 

摘要: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 opposiy 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.

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