A major challenge for drug delivery techniques is to overcome the barrier imposed by the cell membrane. In the past this has been addressed by e.g. permeabilization of the membrane with lipids, electric currents, or toxins, and by physical penetration with microprojectiles. A common issue is physical damage to the cell membrane. Nanotechnology offers the possibility of “nanoinjectors/carriers” that penetrate cell membranes with minimal perturbation. This will require both a more fundamental understanding of how nanoparticles interact with cell membranes and their components, and of how to avoid toxicological side effects via unwanted membrane perturbations. There has been no systematic study of e.g. which parameters determine whether or nor CNTs penetrate membranes, or of the nature of their interaction with different cell organelles. Here we present a systematic study of the effect of CNT (both SWNTs and multi-walled carbon nanotubes, MWNTs) on living prokaryotic (E. coli) and eukaryotic cells (S. cerevissiae) using AFM, and environmental SEM (ESEM). The influence of CNT length and diameter, surface chemistry (e.g. by introduction of carboxylic groups by oxidation), functionalisation by coating with phospholipid bilayers, proteins or double-stranded DNA on these interactions is studied. Acid oxidation and nanotube doping is used for controlling the length and diameter of MWNTs and for modifying their surface chemistry (Burch, Brown, Contera, et al. J. Phys. Chem. C, 2008). We have demonstrated that specific surface chemistry, and CNT diameter are crucial for achieving the coating of CNTs with correctly folded proteins (Burch, Contera, et al., Nanotechnology, 2008) and phosholipid bilayers (Toledo, de Planque, Contera & Ryan, Jap. J. Appl. Phys. 2007, and JACS submitted). The identification of the CNTs inside cells and of their specific interactions with organelles is done with ESEM.
Biophysical Journal Volume 96, Issue 3, Supplement 1, February 2009, Page 51a ISSN: 0006-3495 DOI: 10.1016/j.bpj.2008.12.161