Biotinylated amphiphile-single walled carbon nanotube conjugate for target-specific delivery to cancer cells

Abstract

The present work reports the specific targeting of cancerous cells using a non-covalently water dispersed nanoconjugate of biotinylated amphiphile-single walled carbon nanotube (SWNT). The fundamental approach involves incorporation of the biotin into the architecture of the carbon nanotube (CNT) dispersing agent to develop a multifaceted delivery vehicle having a high colloidal stability, substantial cell viability and targeted specificity towards cancer cells. A three way functionalization strategy was employed to introduce a C-16 hydrophobic segment, polyethylene glycol hydrophilic fragment and biotin as the target-specific unit at the –OH, –COOH and –NH₂ terminals of L-tyrosine, respectively. The newly developed neutral amphiphile exhibited an efficient SWNT dispersion (72%) in water, significant viability of different mammalian cells (Hela, HepG2, CHO and HEK-293) up to 48 h and also media stability. Most importantly, the biotinylated amphiphile-SWNT dispersion successfully transported the fluorescently labelled Cy3-oligoneucleotide (loaded on the surface of CNT) inside the cancerous Hela, HepG2 cells after 3 h of incubation, in contrast to CHO and HEK-293 cells (devoid of overexpressed biotin receptors). The presence of the biotin moiety in the cellular transporters facilitated the internalization of cargo due to the overexpressed biotin receptors in the cancer cells. Importantly, this nanohybrid was also capable of specifically transporting the anticancer drug doxorubicin to cancer cells, which led to the significant killing of Hela cells compared to the normal CHO cells. Thus, the receptor-mediated specific transportation of cargo into cancer cells was possible only due to the biotinylated CNT dispersing agent. To the best of our knowledge this is the first reported amino acid based biotinylated small amphiphilic molecule that non-covalently dispersed SWNTs and the corresponding nanoconjugate showed excellent cell viability, antibiofouling properties and the desired target-specific drug delivery.