When nanoparticles (NPs) are exposed to the biological environment, their surfaces become covered with proteins and biomolecules (e.g. lipids). Here, we report that this protein coating, or corona, reduces the targeting capability of surface engineered NPs by screening the active sites of the targeting ligands.

No abstract

The liver and the mononuclear phagocyte system are a frequent target for engineered nanomaterials, either as a result of particle uptake and spread from primary exposure sites or systemic administration of therapeutic and imaging nanoparticles. In this study, we performed a comparative analysis of the toxicological impact of 29 metal oxide nanoparticles (NPs), some commonly used in consumer products, in transformed or primary Kupffer cells (KCs) and hepatocytes. We not only observed differences between KCs and hepatocytes, but also differences in the toxicological profiles of transition-metal oxides (TMOs, e. g., CoO) versus rare-earth oxide (REO) NPs ( e. g., GdO). While pro-oxidative TMOs induced the activation of caspases 3 and 7, resulting in apoptotic cell death in both cell types, REOs induced lysosomal damage, NLRP3 inflammasome activation, caspase 1 activation, and pyroptosis in KCs. Pyroptosis was accompanied by cell swelling, membrane blebbing, IL-1β release, and increased membrane permeability, which could be reversed by knockdown of the pore forming protein, gasdermin D. Though similar features were not seen in hepatocytes, the investigation of the cytotoxic effects of REO NPs could also be seen to affect macrophage cell lines such as J774A.1 and RAW 264.7 cells as well as bone marrow-derived macrophages. These phagocytic cell types also demonstrated features of pyroptosis and increased IL-1β production. Collectively, these findings demonstrate important mechanistic considerations that can be used for safety evaluation of metal oxides, including commercial products that are developed from these materials.

No abstract

Aluminum-salt-based vaccine adjuvants are prevailingly used in FDA-approved vaccines for the prevention of infectious diseases for over eighty years. Despite their safe applications, the mechanisms regarding how the material characteristics affect the interactions at nano-bio interface and immunogenicity remain unclear. Recently, studies have indicated that the activation of NLRP3 inflammasome plays a critical role in inducing adjuvant effects that are controlled by the inherent shape and hydroxyl contents of aluminum oxyhydroxide (AlOOH) nanoparticles; however, the detailed relationship between surface properties and adjuvant effects for these materials remains unknown. Thus, we engineered AlOOH nanorods (ALNRs) with controlled surface functionalization and charge to assess their effects on the activation of NLRP3 inflammasome in vitro and the potentiation of immunogenicity in vivo. It is demonstrated that NH-functionalized ALNRs exhibited higher levels of cellular uptake, lysosomal damage, oxidative stress, and NLRP3 inflammasome activation than pristine and SOH-functionalized ALNRs in cells. This structure-activity relationship also correlates with the adjuvant activity of the material using ovalbumin (OVA) in a mouse vaccination model. This study demonstrates that surface functionalization of ALNRs is critical for rational design of aluminum-based adjuvants to boost antigen-specific immune responses for more effective and long-lasting vaccination.