Amphiphilic lipid-poly(ethylene glycol) (LPEG) is widely used for the noncovalent functionalization of graphene nanomaterials (GNMs) to improve their dispersion in aqueous solutions for biomedical applications. However, not much is known about the detachment of LPEGs from GNMs and macrophage uptake of dispersed GNMs in relation to the alkyl chain coverage, the PEG coverage, and the linker group in LPEGs. In this study we examined these relationships using single walled carbon nanohorns (SWCNHs). The high coverage of PEG rather than that of alkyl chains was dominant in suppressing the detachment of LPEGs from SWCNHs in protein-containing physiological solution. Correspondingly, the quantity of LPEG-covered SWCNHs (LPEG-SWCNHs) taken up by macrophages decreased at a high PEG coverage. Our study also demonstrated an effect of the ionic group in LPEG on SWCNH uptake into macrophages. A phosphate anionic group in the LPEG induced lower alkyl chain coverage and easy detachment of the LPEG, however, the negative surface charge of LPEG-SWCNHs reduced the uptake of SWCNHs by macrophages. © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.