In Vivo Biointeraction and Alleviation of Toxicity of MWCNTs upon Functionalization with ssDNA in a Caenorhabditis elegans Model

Functionalized carbon nanotubes are recommended as potential drug-delivery tools due to their reduced toxicity and increased solubility or wettability. However, their applications are still restricted because of their dose- and time-dependent toxicity. The conflicting reports regarding toxicity assays of pristine and functionalized multiwalled carbon nanotubes (MWCNTs) in different in vivo and in vitro models inspired us to design a safe drug-releasing device and investigate its applicability in a widely used human-analogous in vivo model. We thereby propose a biocompatible drug-delivery vector that is nontoxic even at higher doses in the Caenorhabditis elegans nematode model. We further carried out a comparative analysis of the various biocompatibility assays of MWCNTs functionalized with inorganic and organic molecules. Synthetic single-stranded DNA (ssDNA) oligonucleotide (5′-GGG-GGG-GGG-G-3′)-functionalized MWCNTs were found to be the most biocompatible and nontoxic even at higher doses (320 µg/mL) of MWCNTs. In contrast, pristine and NH₂-functionalized MWCNT were proven to be toxic at lower doses (20–160 µg/mL) of MWCNTs based on survival, locomotion, reproductive potential, and oxidative-stress-related endpoints. Thus, the order of cytotoxicity in animals was observed to be as follows: pristine MWCNTs > NH₂-functionalized MWCNTs > ssDNA-functionalized MWCNT.