Biomolecular Corona and Mechanisms Involved in Tumor-Targeting and Renal Clearance of Mesoporous Silica Nanoparticles

Mesoporous Silica Nanoparticles (MSNs) have been considered promising for in vivo biomedical applications, such as targeted therapy and diagnostic imaging. However, once nanoparticles are exposed to the biological system, biomolecular corona formed around the nanoparticles can result in unexpected outcomes in terms of therapeutic efficiency, biodistribution, and pharmacokinetics. Therefore, understanding the composition and functionality of protein corona is crucial for nanomedicine development. Nowadays, cancer nanomedicines are widely applied to overcome the low tumor-targeting efficiency of the conventional drug, but the elimination processes of nanoparticles are still unclear. Kidneys, with a filtration threshold of 6 nm for metal-based nanoparticles or proteins defined by the previous investigation, are the major excretion organs in metabolism to remove excess waste in the body.<br/>In this study, we employed LC-MS/MS, SDS-PAGE, DLS, and Zeta potential measurements to identify the protein corona after the <i>in vitro</i> incubation of 25 nm cationic PEGylated MSNs with human plasma and intravenous injection of nanoparticles into the mice. Additional bioinformatics analyses using ClueGo and Ingenuity Pathway Analysis (IPA) revealed altered regulation in crucial pathways. The biodistribution of MSNs in 4T1 breast tumor-bearing BALB/c mice was investigated using immunofluorescence microscopy and a non-invasive <i>in vivo</i> imaging system (IVIS). Our results demonstrated that superior tumor-targeting efficiency could be achieved more simply by reducing protein adsorption but not manipulating protein type on the surface of MSNs. On the other hand, immunofluorescence and TEM visualization showed the localization of PEGylated MSNs in the glomerular basement membrane and mesangial cells. Notably, intact 25 nm cationic PEGylated MSNs were observed in the collective urine. A comprehensive evaluation revealed that the biomolecular mechanisms involved in the excretion of MSNs are through the proximal tubular epithelial cells by caveolae-mediated albumin transcytosis.