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Targeted delivery of a guanidine-pendant Pt(IV)-backboned poly-prodrug by an anisamide-functionalized polypeptide

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Abstract

We describe here a novel targeting polyion complex (Tg-PIC) system for the delivery and intracellular release of cisplatin. Briefly, a guanidinium-pendant Pt(IV)-backboned poly-prodrug termed P(DSP-Gu) is prepared with excellent aqueous solubility, high drug-loading and high potency. To enable prolonged circulation and selective cellular internalization, P(DSP-Gu) is complexed with anisamide-end-capped poly(ethylene glycol)-block-poly(L-phosphotyrosine)-block-poly(L-leucine) (AA-PEG-PpY-PLeu) to yield Tg-PIC via electrostatic coacervation. Tg-PIC is stabilized by hydrogen bonding between phosphate and guanidinium, the PEG corona, and the helical poly(L-leucine) segment forming the hydrophobic core. The anisamide group, a high affinity ligand recognizing the sigma (σ) receptors that are overexpressed on many human malignancies including prostate cancer, is incorporated at the surface of the Tg-PIC for active targeting and efficient internalization. In vitro, the Tg-PICs show targeted and efficient internalization into sigma receptor-positive PC3 cells, and can release toxic Pt(II) species due to the degradation of P(DSP-Gu) under the intracellular reducing conditions. In vivo, the Tg-PICs exhibit superior antitumor efficacy with reduced toxicity. Thus, the system holds considerable promise towards more effective and safe nanomedicine.

Graphical abstract: Targeted delivery of a guanidine-pendant Pt(iv)-backboned poly-prodrug by an anisamide-functionalized polypeptide

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Publication details

The article was received on 20 Sep 2017, accepted on 15 Nov 2017 and first published on 16 Nov 2017


Article type: Paper
DOI: 10.1039/C7TB02513K
Citation: J. Mater. Chem. B, 2017, Advance Article
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    Targeted delivery of a guanidine-pendant Pt(IV)-backboned poly-prodrug by an anisamide-functionalized polypeptide

    S. Li, Y. Wang, J. Zhang, W. Wei and H. Lu, J. Mater. Chem. B, 2017, Advance Article , DOI: 10.1039/C7TB02513K

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