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Title: Enhanced cytotoxicity to cancer cells by mitochondria-targeting MWCNTs containing platinum(IV) prodrug of cisplatin
Authors: Yoong, S.L.
Wong, B.S.
Zhou, Q.L.
Chin, C.F.
Li, J. 
Venkatesan, T. 
Ho, H.K. 
Yu, V.
Ang, W.H. 
Pastorin, G. 
Keywords: 3-Bromopyruvate
Multi-walled carbon nanotubes
Platinum(IV) prodrug
Issue Date: Jan-2014
Citation: Yoong, S.L., Wong, B.S., Zhou, Q.L., Chin, C.F., Li, J., Venkatesan, T., Ho, H.K., Yu, V., Ang, W.H., Pastorin, G. (2014-01). Enhanced cytotoxicity to cancer cells by mitochondria-targeting MWCNTs containing platinum(IV) prodrug of cisplatin. Biomaterials 35 (2) : 748-759. ScholarBank@NUS Repository.
Abstract: Among the arsenal of nano-materials, carbon nanotubes (CNTs) are becoming more prominent due to favorable attributes including their unique shape, which promotes cellular-uptake, and large aspect-ratio that facilitates functionalization of bioactive molecules on their surface. In this study, multi-walled carbon nanotubes (MWCNTs) were functionalized with either mitochondrial-targeting fluorescent rhodamine-110 (MWCNT-Rho) or non-targeting fluorescein (MWCNT-Fluo). Despite structural similarities, MWCNT-Rho associated well with mitochondria (ca. 80% co-localization) in contrast to MWCNT-Fluo, which was poorly localized (ca. 21% co-localization). Additionally, MWCNT-Rho entrapping platinum(IV) pro-drug of cisplatin (PtBz) displayed enhanced potency (IC50=0.34±0.07μM) compared to a construct based on MWCNT-Fluo (IC50≥2.64μM). Concurrently, preliminary invitro toxicity evaluation revealed that empty MWCNT-Rho neither decreased cell viability significantly nor interfered with mitochondrial membrane-potential, while seemingly being partially expelled from cells. Due to its targeting capability and apparent lack of cytotoxicity, MWCNT-Rho complex was used to co-encapsulate PtBz and a chemo-potentiator, 3-bromopyruvate (BP), and the resulting MWCNT-Rho(PtBz+BP) construct demonstrated superior efficacy over PtBz free drug in several cancer cell lines tested. Importantly, a 2-fold decrease in mitochondrial potential was observed, implying that mitochondrial targeting of compounds indeed incurred additional intended damage to mitochondria. © 2013 Elsevier Ltd.
Source Title: Biomaterials
ISSN: 01429612
DOI: 10.1016/j.biomaterials.2013.09.036
Appears in Collections:Staff Publications

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