The cellular uptake and expulsion rates of length-fractionated single-walled carbon nanotubes (SWNT) from 130 to 660 nm in NIH-3T3 cells were measured via single particle tracking of their intrinsic photoluminescence. We develop a quantitative model to correlate endocytosis rate with nanoparticle geometry that accurately describes this data set and also literature results for Au nanoparticles. The model asserts that nanoparticles cluster on the cell membrane to form a size sufficient to generate a large enough enthalpic contribution via receptor ligand interactions to overcome the elastic energy and entropic barriers associated with vesicle formation. Interestingly, the endocytosis rate constant of SWNT (10(-3) min(-1)) is found to be nearly 1000 times that of Au nanoparticles (10(-6) min(-1)) but the recycling (exocytosis) rate constants are similar in magnitude (10(-4) to 10(-3) min(-1)) for poly(d,l-lactide-co-glycolide), SWNT, and Au nanoparticles across distinct cell lines. The total uptake of both SWNT and Au nanoparticles is maximal at a common radius of 25 nm when scaled using an effective capture dimension for membrane diffusion. The ability to understand and predict the cellular uptake of nanoparticles quantitatively should find utility in designing nanosystems with controlled toxicity, efficacy, and functionality.

Molecular recognition is central to the design of therapeutics, chemical catalysis and sensors. Motifs for doing so most commonly involve biological structures such as antibodies and aptamers. The key to such biological recognition consists of a folded and constrained heteropolymer that, via intra-molecular forces, forms a unique three dimensional structure that creates a binding pocket or an interface able to recognize a specific molecule. In this work, we demonstrate that synthetic heteropolymers can be alternatively constrained by adsorption around a nanoparticle, and specifically a single walled carbon nanotube (SWNT), forming a corona phase and resulting in a new form of molecular recognition of specific molecules. The phenomenon is shown to be generic, with new heteropolymer recognition complexes demonstrated for three distinct examples: Riboflavin, l-thyroxine, and estradiol, each predicted using a 2D thermodynamic model of surface interactions. The dissociation constants are continuously tunable by perturbing the chemical structure of the heteropolymer. Moreover, these complexes can be used as new types of spatial-temporal sensors based on modulation of SWNT photoemission in the near-infrared, as we show by tracking riboflavin diffusion in murine macrophages.

Over 10000 individual trajectories of nonphotobleaching single-walled carbon nanotubes (SWNT) were tracked as they are incorporated into and expelled from NIH-3T3 cells in real time on a perfusion microscope stage. An analysis of mean square displacement allows the complete construction of the mechanistic steps involved from single duration experiments. We observe the first conclusive evidence of SWNT exocytosis and show that the rate closely matches the endocytosis rate with negligible temporal offset. We identify and study the endocytosis and exocytosis pathway that leads to the previously observed aggregation and accumulation of SWNT within the cells.