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In vitro controlled release of cisplatin from gold-carbon nanobottles via cleavable linkages

Authors Li J, Yoong SL, Goh WJ, Czarny B, Yang Z, Poddar K, Dykas M, Patra A, Thirumalai Venkatesan T, Panczyk T, Lee C, Pastorin G

Received 5 August 2015

Accepted for publication 12 October 2015

Published 15 December 2015 Volume 2015:10(1) Pages 7425—7441


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Govarthanan Muthusamy

Peer reviewer comments 3

Editor who approved publication: Prof. Dr. Thomas J Webster

Jian Li,1 Sia Lee Yoong,2 Wei Jiang Goh,2 Bertrand Czarny,1 Zhi Yang,1 Kingshuk Poddar,2,3 Michal M Dykas,2,3 Abhijeet Patra,2,3 T Venkatesan,2,3 Tomasz Panczyk,4 Chengkuo Lee,5 Giorgia Pastorin1–3

1Department of Pharmacy, National University of Singapore, 2NUS Graduate School for Integrative Sciences and Engineering, Centre for Life Sciences (CeLS), 3NUSNNI-NanoCore, National University of Singapore, Singapore; 4Institute of Catalysis and Surface Chemistry, Polish Academy of Sciences, Cracow, Poland; 5Department of Electrical and Computer Engineering, National University of Singapore, Singapore

Abstract: Carbon nanotubes’ (CNTs) hollow interior space has been explored for biomedical applications, such as drug repository against undesirable inactivation. To further devise CNTs as smart material for controlled release of cargo molecules, we propose the concept of “gold-carbon nanobottles”. After encapsulating cis-diammineplatinum(II) dichloride (cisplatin, CDDP) in CNTs, we covalently attached gold nanoparticles (AuNPs) at the open-tips of CNTs via different cleavable linkages, namely hydrazine, ester, and disulfide-containing linkages. Compared with our previous study in which more than 80% of CDDP leaked from CNTs in 2 hours, AuNPs were found to significantly decrease such spontaneous release to <40%. In addition, CDDP release from AuNP-capped CNTs via disulfide linkage was selectively enhanced by twofolds in reducing conditions (namely with 1 mM dithiothreitol [DTT]), which mimic the intracellular environment. We treated human colon adenocarcinoma cells HCT116 with our CDDP-loaded gold-carbon nanobottles and examined the cell viability using lactate dehydrogenase assay. Interestingly, we found that our nanobottles with cleavable disulfide linkage exerted stronger cytotoxic effect in HCT116 compared with normal human fetal lung fibroblast cells IMR-90. Therefore, we infer that our nanobottles strategy with inbuilt disulfide linkage could attain selective release of payload in highly reductive tumor tissues while avoiding collateral damage to normal tissues.

Keywords: carbon nanotubes, surface functionalization, cleavable bonds, cisplatin, drug delivery

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