Cell-type specific and cytoplasmic targeting of PEGylated carbon nanotube-based nanoassemblies.
In this paper we report the fabrication of a multivalent, cell-type specific and cytoplasmic delivery system based on single-walled carbon nanotubes. The latter were functionalized through adsorption of phospholipids terminated by biotinylated PEG chains functionalized with fluorochrome-coupled neutravidin, and subsequently with antibodies (anti-CD3epsilon and anti-CD28) for T cell receptor post-signaling endocytosis and a synthetic fusogenic polymer for disruption of lysosomal compartments. The biomimetic nanoassemblies were composed by PEGylated individual/very small bundles of carbon nanotubes having an average length and a standard deviation of 176 nm and 77 nm, respectively. The nanoassemblies were stably dispersed under physiological conditions, visible by conventional optical and confocal microscopy and specifically targeted to T cells both in vitro and in living animals. The addition of a fusogenic polymer to the nanoassemblies did not affect the cellular uptake and allowed the release into the cytosol of the targeted cells both in vitro and in the animals. The present manuscript is the first report about the cytoplasmic delivery of carbon nanotubes in a specific cell type in intact animals and paves the way for their use as in vivo intracellular delivery systems.
Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Matthew H
MH
Cato
Federica
F
D'Annibale
David M
DM
Mills
Fabio
F
Cerignoli
Marcia I
MI
Dawson
Enrico
E
Bergamaschi
Nunzio
N
Bottini
Andrea
A
Magrini
Antonio
A
Bergamaschi
Nicola
N
Rosato
Robert C
RC
Rickert
Tomas
T
Mustelin
Massimo
M
Bottini
D000818:Animals; D003593:Cytoplasm / Q000378:metabolism*; D004705:Endocytosis; D005434:Flow Cytometry; D051379:Mice; D018625:Microscopy, Atomic Force; D018613:Microscopy, Confocal; D037742:Nanotubes, Carbon; D011092:Polyethylene Glycols / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D013601:T-Lymphocytes / Q000378:metabolism
D037742:Nanotubes, Carbon; D011092:Polyethylene Glycols