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.

Genetic Engineering of Mesenchymal Stem Cells to Induce Their Migration and Survival

“…This would imply a need to use advanced techniques [ 93 ], modifying MSCs with multiples genes, at the same time ensuring the effective expression of each of them, and perhaps in some cases providing some sort of sequential induction of introduced gene expression. This aim might be achieved by the employment of different genetic material loaded nanostructures that, depending on the nanostructure composition, would potentially release their contents into the cytoplasm with different speed [ 94 , 95 ].…”

Coadsorption of Doxorubicin and Selected Dyes on Carbon Nanotubes. Theoretical Investigation of Potential Application as a pH-Controlled Drug Delivery System

“…On the other hand, there are numerous studies showing encapsulation of platinum-based drugs in the inner space of CNTs. The release rate in such systems is often controlled by formation of removable caps locking the nanotube tips. , …”