Carboxylated versus bisphosphonate SWCNT: Functionalization effects on the biocompatibility and in vivo behaviors in tumor-bearing mice

Single-walled carbon nanotubes (SWCNT) are raising interest in biomedical field, as a drug delivery system, due to their large payload capacity and rich surface chemistry that allows attaching molecules. Generally, carbon nanotubes, without any surface modifications are cytotoxic to certain mammalian cells. However, after their functionalization, they become biocompatible and non-immunogenic. Thus, the aim of this work was to evaluate the effect of functionalization groups on the biocompatibility of SWCNT in vitro, as well as on its biodistribution in tumor-bearing mice. In this approach, carboxylate and bisphosphonate functionalized SWCNT were successfully synthesized and characterized by Raman, FTIR, and TGA techniques. The in vitro cytotoxicity against HEK-293 cells, and hemolysis assay were carried out and the results revealed important biocompatibility profile for both functionalized nanotubes. Furthermore, both types of SWCNT were successful radiolabeled with technetium-99 m, and biodistribution studies were conducted in Ehrlich tumor-bearing Swiss mice, showing higher tumor uptake by bisphosphonated SWCNT compared to carboxylated nanotubes. Moreover, acute toxicity study was performed in healthy Swiss mice revealing that none of the nanotubes displayed hematological, hepatic or renal toxicity. From all obtained results, the bisphosphonate functionalized SWCNT can be considered a plausible and alternative drug delivery platform for theranostic and therapeutics purposes.