Phosphatase-triggered cell-selective release of a Pt(iv)-backboned prodrug-like polymer for an improved therapeutic index.
Biomater Sci
; 5(8): 1558-1566, 2017 Jul 25.
Article
em En
| MEDLINE
| ID: mdl-28181619
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.
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1
Base de dados:
MEDLINE
Assunto principal:
Platina
/
Polímeros
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Pró-Fármacos
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Monoéster Fosfórico Hidrolases
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Índice Terapêutico
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article