470252 Non-Covalent Functionalization of Single Wall Carbon Nanotubes with Engineered Proteins for Targeted Subcellular Delivery
We have used similar techniques to show cellular uptake of bovine serum albumin (BSA)-coated SWCNTs within cells. We see localization of SWCNTs-BSA within the endosomal and metabolic processing compartments. Similarly to LB1, BSA is a small globular protein, and the hydrophobic cleft of the BSA binds to SWCNTs. BSA has smaller hydrophobic regions, independent of the hydrophobic cleft, that can be loaded with drugs or fluorophores. In vitro, we show that denaturation or enzymatic processing of the BSA releases the small molecules. SWCNTs-BSA in which the BSA are pre-loaded with rhodamine drastically increases small molecule delivery in culture. We have determined spatial and concentration distribution of rhodamine within the cells, and signal is both coincident and distinct from SWCNTs as measured by NIR fluorescence and Raman. We demonstrate efficacy of this approach by delivering a fluorescent chemotherapeutic drug daunomycin that reduces proliferation in cancer cells. Together, our results demonstrates a pathway to increase the delivery of a wide variety of drugs to cells through SWCNTs coated with albumin pre-loaded with drug molecules.
The complexity of protein structures allows for multimodal modification and manipulation of cellular processes in addition to SWCNT dispersion. The modification of native cellular proteins as non-covalent dispersing agents to provide specific transport opens new possibilities to utilize both SWCNT and protein properties for multifunctional subcellular targeting applications. Specifically, nuclear targeting will allow delivery of anticancer therapies, genetic treatments, or DNA, which in turn will promote development of novel cellular therapies. Using the transport properties of albumins and intracellular processing by enzymes allows delivery of native molecules and drugs.
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