Serum Protein Adsorption Enhances Active Leukemia Stem Cell Targeting of Mesoporous Silica Nanoparticles

The functionalization of nanoparticles with a ligand targeting receptors overexpressed by the target cells is a commonly used strategy when aiming at nanoparticle-based, cell type-specific drug delivery.1-4 However, the influence of particle surface chemistry on the targetability has received much less attention. The surface charge is known to directly or indirectly affect the nanoparticle cellular uptake kinetics by influencing serum protein adsorption.5-7 Thus, it is fair to assume that both the specificity and cellular uptake kinetics of targeted nanoparticles are influenced by the nanoparticle charge, both of which are important parameters for controlling cell-specific drug delivery efficiency. We therefore studied the influence of the surface chemistry of mesoporous silica nanoparticles (MSNs) carrying identical amounts of a specific antibody (anti-B220) on the selectivity toward B220-positive leukemia stem cells. The uptake by these cells was higher compared to the nanoparticle uptake by B220-negative leukemia stem cells, demonstrating uptake specificity. In addition, the adsorption of serum proteins onto the differently charged MSNs was studied by SDS-PAGE. Interestingly, the highest selectivity was not observed for the MSNs with the lowest level of serum protein adsorption, which suggests that proteins present in the protein corona of the MSNs may positively influence the selective uptake of targeted nanoparticles. For the particles exhibiting the highest selectivity, successful selective delivery of cargo to the B220-positive cells was demonstrated. Taken together, our results indicate that nanoparticle surface charge and adsorption of serum proteins is an important factor for enhancing selectivity in targeted delivery of drugs using nanoparticulate vectors, an observation tentatively attributed to enhanced cellular internalization kinetics in the presence of adsorbed serum proteins on the nanoparticles.