Chitosan−Cholesterol-Based Cellular Delivery of Anionic Nanoparticles

Nanoparticle-based cellular probes are emerging as an alternative for molecular probes. However, cellular interaction and uptake of nanoprobes strongly depends on their surface chemistry, and the delivery of anionic nanoparticles is relatively difficult. Herein, we report cholesterol-modified chitosan oligosaccharide as a nontoxic reagent that is able to deliver different anionic nanoparticles into the cell. The cationic chitosan backbone of the reagent assists their electrostatic binding with the anionic nanoparticle, and the hydrophobic cholesterol component induces cellular interaction/uptake. The optimum amount of cholesterol is decisive as an effective reagent—high cholesterol per chitosan reduces their water solubility, while low cholesterol per chitosan provides poor performance, similar to chitosan. Different anionic nanoparticles of hydrodynamic diameter 20−50 nm such as polyacrylate coated anionic quantum dot (QD) and iron oxide nanoparticle are effectively delivered into cells. The developed chitosan−cholesterol reagent is easy to prepare, is nontoxic, requires a low dose for nanoparticle delivery, and can be used for the cellular delivery of other anionic nanoparticles.