Misfolded Proteins Direct Nanoparticles

In biological fluids, nanoparticles end up coated with a mixture of proteins and lipids, a process that determines the ultimate destination of the nanoparticles. By exploiting that so-called protein corona, Paul Wentworth Jr. of the University of Oxford and Scripps Research Institute and Oxford graduate students Kanlaya Prapainop and Daniel P. Witter have shown they can direct diagnostic nanoparticles to specific cell types (J. Am. Chem. Soc., DOI: 10.1021/ja300537u). The researchers chemically modified the surface of CdSe/ZnS quantum dots with cholesterol 5,6-secosterol atheronal-B, an inflammatory metabolite that triggers misfolding of apolipoprotein B in the corona. The conformational change exposes binding sites in apolipoprotein B for receptors on the surface of macrophages, which take up the nanoparticles via receptor-mediated endocytosis. Different cell types can be targeted by using different molecules to expose binding sites for other receptors, the researchers note. Kenneth A. Dawson, an expert on protein-nanoparticle interactions at University College Dublin, calls such reprogramming “a creative and inventive way of thinking of the problem—working with the corona, not trying to eliminate it but using it wisely.”