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복잡계자기조립연구단
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Self-assembled nanocomplex between polymerized phenylboronic acid and doxorubicin for efficient tumor-targeted chemotherapy

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Title
Self-assembled nanocomplex between polymerized phenylboronic acid and doxorubicin for efficient tumor-targeted chemotherapy
Author(s)
Junseok LEE; Jinhwan KIM; Yeong Mi LEE; Dongsik PARK; Sooseok IM; Eun Ho SONG; Hansoo PARK; Won Jong KIM
Subject
Anticancer drugs, ; Boronic ester, ; Doxorubicin, ; Nano-sized complex, ; PH-responsive, ; Self-assembly
Publication Date
2017-06
Journal
ACTA PHARMACOLOGICA SINICA, v.38, no.6, pp.848 - 858
Publisher
Nature Publishing Group
Abstract
Since the discovery that nano-scaled particulates can easily be incorporated into tumors via the enhanced permeability and retention (EPR) effect, such nanostructures have been exploited as therapeutic small molecule delivery systems. However, the convoluted synthetic process of conventional nanostructures has impeded their feasibility and reproducibility in clinical applications. Herein, we report an easily prepared formulation of self-assembled nanostructures for systemic delivery of the anti-cancer drug doxorubicin (DOX). Phenylboronic acid (PBA) was grafted onto the polymeric backbone of poly(maleic anhydride). pPBA-DOX nanocomplexes were prepared by simple mixing, on the basis of the strong interaction between the 1,3-diol of DOX and the PBA moiety on pPBA. Three nanocomplexes (1, 2, 4) were designed on the basis of [PBA]:[DOX] molar ratios of 1:1, 2:1, and 4:1, respectively, to investigate the function of the residual PBA moiety as a targeting ligand. An acid-labile drug release profile was observed, owing to the intrinsic properties of the phenylboronic ester. Moreover, the tumor-targeting ability of the nanocomplexes was demonstrated, both in vitro by confocal microscopy and in vivo by fluorescence imaging, to be driven by an inherent property of the residual PBA. Ligand competition assays with free PBA pre-treatment demonstrated the targeting effect of the residual PBA from the nanocomplexes 2 and 4. Finally, the nanocomplexes 2 and 4, compared with the free DOX, exhibited significantly greater anti-cancer effects in vitro and even in vivo. Our pPBA-DOX nanocomplex enables a new paradigm for self-assembled nanostructures with potential biomedical applications. © The Author(s) 2017
URI
https://pr.ibs.re.kr/handle/8788114/3661
DOI
10.1038/aps.2017.16
ISSN
1671-4083
Appears in Collections:
Center for Self-assembly and Complexity(복잡계 자기조립 연구단) > 1. Journal Papers (저널논문)
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