Functional surface modifications impact on the in vitro/in vivo toxicity and intracellular internalization behavior of mesoporous silica nanoparticles

The surface properties of nanocarriers, including morphology, charge and surface modification are closely associated with their in vivo toxicity, biodistribution and bioavailability, which further affect the therapeutic effect. Herein, a series of in vitro and in vivo studies, including hemolysis, protein adsorption, cytotoxicity, cellular uptake and in vivo acute toxicity were performed to investigate the influences of surface properties on the biocompatibility and intracellular internalization behavior of functionalized degradable dendritic mesoporous silica nanoparticles (DDMSNs). The results illustrated that hyaluronic acid-modified DDMSNs (DDMSNs-NH2-HA) nanocarriers showed lower hemolysis, non-specific protein adsorption and in vitro cytotoxicity compared to DDMSNs and aminated DDMSNs (DDMSNs-NH2). The HA-mediated efficient intracellular internalization and significant accumulation of DDMSNs-NH2-HA in A549 cells was observed by cellular uptake assays. Furthermore, compared to DDMSNs and DDMSNs-NH2 groups, no significant pathological abnormalities were found in the hematoxylin and eosin-stained sections of key organs induced by DDMSNs-NH2-HA nanocarriers for in vivo toxicity, indicating that the improvement of nanocarriers' biocompatibility arose from HA modification. This work explored the influencing mechanism of surface properties on biological toxicity and intracellular internalization behavior of nanocarriers in vitro and in vivo, which provided an insight into the design of biocompatible nano-DDS by rational surface modifications.