PEG-derivatized birinapant as a nanomicellar carrier of paclitaxel delivery for cancer therapy.

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ID: 3048
2019
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Abstract
A novel triblock amphiphilic copolymer (PAL-PEG-Birinapant) was designed and synthesized as a dual-functional micellar carrier utilizing birinapant (an inhibitor of inhibitor-of-apoptosis proteins) as a pH-sensitive segment and inhibitor-of-apoptosis proteins-targeting ligand. The mixed micelles comprised of PAL-PEG-Birinapant (PPB) and mPEG2k-PDLLA2k (MPP), named as PPB/MPP (2/1,w/w) micelles were developed for enhanced solubility and antitumor potency of hydrophobic drugs as paclitaxel (PTX). In vitro cell viability and cytotoxicity studies revealed that the PTX-loaded PPB/MPP micelles were more potent than the commercial PTX formulation (Taxol), as well as the in vitro cell apoptosis study. Clear differences in the intracellular uptake of free coumarin-6 (C6) solution and C6-loaded PPB/MPP micelles were observed and indicated that the PPB/MPP micelles could efficiently deliver chemical compound into tumor cells. PPB copolymer and PTX-loaded PPB/MPP micelles demonstrated an excellent safety profile with a maximum tolerated dose (MTD) of above 1.2 g copolymer/kg and above 100 mg PTX/kg in mice respectively in contrast to 20˜24 mg/kg of Taxol®. The near infrared (NIR) fluorescence imaging showed that PPB/MPP micelles persisted for a relatively long time in the circulation and accumulated preferentially in tumor tissue. Moreover, PTX loaded PPB/MPP micelles significantly inhibited the tumor growth both in MDA-MB-231 and Ramos cancer xenograft mice models without obvious toxicity. Collectively, our study presents a new dual-functional micelles that improve the therapeutic efficacy of PTX in vitro and in vivo.
Reference Key
shu2019pegderivatizedcolloids Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Shu, Xiaoming;Zhu, Zhejiang;Cao, Dan;Zheng, Li;Wang, Fang;Pei, Heying;Wen, Jiaolin;Yang, Jianhong;Li, Dan;Bai, Peng;Tang, Minghai;Ye, Haoyu;Peng, Aihua;Li, Weimin;Chen, Lijuan;
Journal colloids and surfaces b, biointerfaces
Year 2019
DOI
S0927-7765(19)30490-4
URL
Keywords Keywords not found

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