title: In vitro controlled release of cisplatin from gold-carbon nanobottles via cleavable linkages.
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.
authors.affiliation: Department of Pharmacy, National University of Singapore, Singapore.
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.affiliation: NUS Graduate School for Integrative Sciences and Engineering, Centre for Life Sciences (CeLS), National University of Singapore, Singapore.
authors.forename: Sia Lee
authors.initials: SL
authors.lastname: Yoong
authors.affiliation: NUS Graduate School for Integrative Sciences and Engineering, Centre for Life Sciences (CeLS), National University of Singapore, Singapore.
authors.forename: Wei Jiang
authors.initials: WJ
authors.lastname: Goh
authors.affiliation: Department of Pharmacy, National University of Singapore, Singapore.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Czarny
authors.affiliation: Department of Pharmacy, National University of Singapore, Singapore.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yang
authors.affiliation: NUS Graduate School for Integrative Sciences and Engineering, Centre for Life Sciences (CeLS), National University of Singapore, Singapore ; NUSNNI-NanoCore, National University of Singapore, Singapore.
authors.forename: Kingshuk
authors.initials: K
authors.lastname: Poddar
authors.affiliation: NUS Graduate School for Integrative Sciences and Engineering, Centre for Life Sciences (CeLS), National University of Singapore, Singapore ; NUSNNI-NanoCore, National University of Singapore, Singapore.
authors.forename: Michal M
authors.initials: MM
authors.lastname: Dykas
authors.affiliation: NUS Graduate School for Integrative Sciences and Engineering, Centre for Life Sciences (CeLS), National University of Singapore, Singapore ; NUSNNI-NanoCore, National University of Singapore, Singapore.
authors.forename: Abhijeet
authors.initials: A
authors.lastname: Patra
authors.affiliation: NUS Graduate School for Integrative Sciences and Engineering, Centre for Life Sciences (CeLS), National University of Singapore, Singapore ; NUSNNI-NanoCore, National University of Singapore, Singapore.
authors.forename: T
authors.initials: T
authors.lastname: Venkatesan
authors.affiliation: Institute of Catalysis and Surface Chemistry, Polish Academy of Sciences, Cracow, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Panczyk
authors.affiliation: Department of Electrical and Computer Engineering, National University of Singapore, Singapore.
authors.forename: Chengkuo
authors.initials: C
authors.lastname: Lee
authors.affiliation: Department of Pharmacy, National University of Singapore, Singapore ; NUS Graduate School for Integrative Sciences and Engineering, Centre for Life Sciences (CeLS), National University of Singapore, Singapore ; NUSNNI-NanoCore, National University of Singapore, Singapore.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Pastorin
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D003692:Delayed-Action Preparations / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006046:Gold / Q000737:chemistry*; D045325:HCT116 Cells; D006801:Humans; D037742:Nanotubes, Carbon / Q000737:chemistry* / Q000648:ultrastructure
chemical_list: D003692:Delayed-Action Preparations; D037742:Nanotubes, Carbon; D006046:Gold; D002945:Cisplatin
keywords: carbon nanotubes; cisplatin; cleavable bonds; drug delivery; surface functionalization