Mesoscopic metal nanoparticles doubly functionalized with natural and engineered lipidic dispersants for therapeutics.

Surface engineering of mesoscopic metal nanoparticles to increase biocompatibility and cell interaction is important for improvement of their therapeutic properties. Here, we describe a strategy to stabilize mesoscopic metal nanoparticles and to enhance their cell interaction by stepwise addition of (Z)-9-octadecenoate (oleate) and a cell-penetrating peptide-fused high-density lipoprotein (cpHDL). Oleate replaces a cytotoxic dispersant on the surface of gold nanorods (AuNRs), which enables subsequent cpHDL binding without causing aggregation. Notably, these two lipidic dispersants are probably intercalated on the surface. This procedure was also used to stabilize 20 nm spherical gold nanoparticles and 40 nm aggregates of 10 nm magnetite nanoparticles. cpHDL-bound AuNRs were internalized greater than 80 times more efficiently than poly(ethylene glycol)-conjugated AuNRs and were able to elicit cancer cell photoablation.