Journal
INTERNATIONAL JOURNAL OF NANOMEDICINE
Volume 10, Issue -, Pages 7425-7441Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/IJN.S93810
Keywords
carbon nanotubes; surface functionalization; cleavable bonds; cisplatin; drug delivery
Funding
- National University of Singapore, Department of Pharmacy [R-148-000-164-112, N-148-000-009-001]
- Ministry of Education of Singapore [MOE2011-T21-1201-P09, R-144-000-306-112]
- NUS Graduate School for Integrative Sciences and Engineering graduate fellowship
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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.
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