Improved cellular uptake of functionalized single-walled carbon nanotubes

Abstract

Single-walled carbon nanotubes (SWNTs) due to their unique structural and physicochemical properties, have been proposed as delivery systems for a variety of diagnostic and therapeutic agents. However, SWNTs have proven difficult to solubilize in aqueous solution, limiting their use in biological applications. In an attempt to improve SWNTs' solubility, biocompatibility, and to increase cell penetration we have thoroughly investigated the construction of carbon scaffolds coated with aliphatic carbon chains and 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, C(18)H(37)OH; 816 nmol mg(-1) of SWNTs). Subsequently, SWNTs-COOC(18)H(37) derivatives were coated with phosphatidylethanolamine (PE) or -serine (PS) phospholipids obtaining micelle-like structures. We found that cellular uptake of these constructs by phagocytic cells occurs via an endocytotic mechanism for constructs larger than 400 nm while occurs via diffusion through the cell membrane for constructs up to 400 nm. The material that enters the cell by phagocytosis is actively internalized by macrophages and localizes inside endocytotic vesicles. In contrast the material that enters the cells by diffusion is found in the cell cytosol. In conclusion, we have realized new biomimetic constructs based on alkylated SWNTs coated with phospholipids that are efficiently internalized by different cell types only if their size is lower than 400 nm. These constructs are not toxic to the cells and could now be explored as delivery systems for non-permeant cargoes.

Toxicological assessment of multi-walled carbon nanotubes on A549 human lung epithelial cells

“…Moreover, CNTs cellular uptake may occur through passive diffusion (nanopenetration) or by the mechanisms of endocytosis/phagocytosis (Firme and Bandaru, 2010). However, the efficient uptake of nano-needles depends on their hydrophobicity (Antonelli et al, 2010) and in A549 cell line the endocytosis is caveolae and/or clathrin-induced (Guo et al, 2012).…”

Pulmonary DWCNT exposure causes sustained local and low-level systemic inflammatory changes in mice

“…Due to their one-dimensional nanostructure, carbon nanotubes (CNTs) have shown promise to facilitate cellular delivery and to overcome biological barriers [1]. In particular, single wall carbon nanotubes (SWCNTs), which consist of only one carbon layer and thereby feature the smallest tube diameter of only 1-2 nm, seem advantageous for drug delivery to intracellular targets, since these CNT specimens may enter the cells by non-specific, physical penetration of the cell membrane without cytotoxic response [2][3][4]. On the other hand, the pharmaceutical application of SWCNT is limited due to difficulties in covalent surface functionalization without causing collateral damage to the carbon backbone and thereby changing the tube morphology and surface chemistry.…”

Radio‐Labeled Nanoparticles for Biomedical Imaging

“…CNTs have also been reported to localize on cells via different routes based on their layering and size. Small CNTs with lengths less than 400 nm can be taken up into cells by diffusion, while larger CNTs enter cells by endocytosis [77]. based on the number of layers, mWNTs are often localized on the cell surface, while the SWNTs are internalized into the nucleus (short SWNTs) or cytoplasm (long SWNTs) [78,79].…”