Improved cellular uptake of functionalized single-walled carbon nanotubes

Abstract

Single-walled carbon nanotubes (SWNTs) due to their unique structural andphysicochemical properties, have been proposed as delivery systems for a variety ofdiagnostic and therapeutic agents. However, SWNTs have proven difficult to solubilize inaqueous solution, limiting their use in biological applications. In an attempt to improveSWNTs’ solubility, biocompatibility, and to increase cell penetration we have thoroughlyinvestigated the construction of carbon scaffolds coated with aliphatic carbon chainsand phospholipids to obtain micelle-like structures. At first, oxidized SWNTs (2370 ± 30 nmol mg − 1 of SWNTs) were covalently coupled with an alcoholic chain (stearyl alcohol,C18H37OH;816 nmol mg − 1 of SWNTs).Subsequently, SWNTs–COOC18H37 derivatives were coated with phosphatidylethanolamine (PE) or -serine (PS) phospholipidsobtaining micelle-like structures. We found that cellular uptake of these constructs byphagocytic cells occurs via an endocytotic mechanism for constructs larger than 400 nmwhile occurs via diffusion through the cell membrane for constructs up to 400 nm. Thematerial that enters the cell by phagocytosis is actively internalized by macrophages andlocalizes inside endocytotic vesicles. In contrast the material that enters the cells bydiffusion is found in the cell cytosol. In conclusion, we have realized new biomimeticconstructs based on alkylated SWNTs coated with phospholipids that are efficientlyinternalized by different cell types only if their size is lower than 400 nm. These constructsare not toxic to the cells and could now be explored as delivery systems for non-permeantcargoes.