Stealthiness and Hematocompatibility of Gold Nanoparticles with Pre-Formed Protein Corona

Studies have established that a serum protein corona pre-formed around gold nanorods (NRs) could be exploited for loading photosensitizers and chemotherapeutics to result in efficient cell kill in vitro with an extremely low dose. In this study, we further demonstrated that pre-forming a serum protein corona (PC) around citrate-capped NRs (NR-Cit) to form NR-PC conferred them stealth property and high hematocompatibility similar to the common strategy of PEGylating NRs, which would otherwise not be able to evade the immune system. Specifically, the NR-PC caused minimal complement activation with significantly lower formation of the terminal complement complex SC5b-9 measured in human serum containing NR-PC, and this resulted in low uptake by phagocytic U937 monocytes of 5.9% of the initial gold dose compared to 55.8% of NR-Cit. In addition, NR-PC exhibited very low hemolytic activity of less than 0.2% hemolysis with no observable effect on RBC morphology as opposed to 0.6% for NR-Cit at the same concentration of 1 nM NRs. Furthermore, we showed that the high hematocompatibility and stealth property of NR-PC were maintained even after the loading of small molecules, photosensitizer Chlorine e6 (Ce6), into the protein corona, thus further establishing the potential clinical relevance of exploiting the inevitably formed serum protein corona on nanoparticles as an effective delivery vector for small molecular therapeutics.