Adhesin Antibody-Grafted Mesoporous Silica Nanoparticles Suppress Immune Escape for Treatment of Fungal Systemic Infection.

Abstract

Life-threatening systemic fungal infections caused byare significant contributors to clinical mortality, particularly among cancer patients and immunosuppressed individuals. The evasion of the immune response facilitated by fungal surface components enables fungal pathogens to evade macrophage attacks and to establish successful infections. This study developed a mesoporous silica nanoplatform, i.e., MSNP-EAP1Ab, which is composed of mesoporous silica nanoparticles grafted with the antibody ofsurface adhesin Eap1. The activity of MSNP-EAP1Ab againstimmune escape and infection was then evaluated by using the cell interaction model and the mouse systemic infection model. During interaction betweencells and macrophages, MSNP-EAP1Ab significantly inhibited fungal immune escape, leading to the enhanced phagocytosis of fungal cells by macrophages, with phagocytosis rates increasing from less than 8% to 14%. Furthermore, after treatment of the-infected mice, MSNP-EAP1Ab drastically prolonged the mouse survival time and decreased the kidney fungal burden from >30,0000 CFU/g kidney to <100 CFU/g kidney, indicating the rapid recognition and killing of the pathogens by immune cells. Moreover, MSNP-EAP1Ab attenuated kidney tissue inflammation, with remarkable attenuation of renal immune cell accumulation. This study presents an innovative nanoplatform that targets theadhesin, offering a promising approach for combatting systemic fungal infections.