A Pt(iv)-mediated polymer architecture for facile and stimuli-responsive intracellular gene silencing with chemotherapy

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Title
A Pt(iv)-mediated polymer architecture for facile and stimuli-responsive intracellular gene silencing with chemotherapy
Author(s)
Sungjin Jung; Jinhwan Kim; Swapan Pramanick; Hyeongmok Park; Hyori Lee; Junseok Lee; Won Jong Kim
Publication Date
2018-12
Journal
BIOMATERIALS SCIENCE, v.6, no.12, pp.3345 - 3355
Publisher
ROYAL SOC CHEMISTRY
Abstract
Conventional chemotherapy has been impeded by the inherent characteristics of cancer including fast mutagenesis and drug resistance; thus a combination therapy consisting of multiple therapeutic strategies has attracted much attention. However, the loading processes of multiple therapeutic molecules affect each other; thus the development of a nanocarrier that enables independent loading of the cargo molecules has been demanded. Herein, we report an ingeniously designed Pt(iv)-mediated polymeric architecture (Pt-PA) for combinatorial gene and chemotherapy to address the issue, prepared by crosslinking a cationic polymer (polyethylenimine, PEI) with a Pt(iv) prodrug. Therapeutic siRNA (anti-BCL2) was simply loaded by electrostatic interaction to form a stable nanocomplex. In the cellular study, the simultaneous release of both the active Pt(ii) drug and siRNA was monitored under the intracellular reducing environment, driven by dissociation of the polymer architecture due to an inherent characteristic of the Pt(iv) crosslinker. Therefore, an enhanced gene silencing effect and an anticancer effect were observed. Furthermore, in the animal study, an improved therapeutic effect of the nanocomplex was observed, which can be explained by tumor targeting via the EPR effect, and enhanced drug and siRNA release at the intracellular environment simultaneously. Taken together, the overall results from in vitro and in vivo studies strongly suggest the therapeutic potential of our precisely designed Pt(iv)-mediated polymer architecture. (C) 2018 The Royal Society of Chemistry
URI
https://pr.ibs.re.kr/handle/8788114/5318
ISSN
2047-4830
Appears in Collections:
Center for Self-assembly and Complexity(복잡계 자기조립 연구단) > Journal Papers (저널논문)
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