Mesoporous Silica Nanoparticles: Insights into Property-Function Relationships and Their Toxicological Implications

Abstract

Mesoporous silica nanoparticles (MSNs) offer several advantages and features for drug delivery, including large surface areas, customisable pore sizes, controllable particle sizes and shapes, dual-functional surfaces, ease of synthesis, and chemical and thermal stability. These nanoparticles show promise as carriers that encapsulate and protect toxic, delicate, soluble, or insoluble therapeutic molecules or imaging agents from premature release. Given the immense potential of MSNs in nanomedicine-based therapeutics, an in-depth toxicity assessment of these materials, separate from the drug payload, must be conducted to ensure the safety and efficacy of these drug delivery vehicles. This review systematically examines how the structural classification of MSNs and physicochemical properties, including particle size, surface charge, shape, pore size, surface coating, crystallinity and functionalisation, govern their toxicological profile. It critically analyses systemic toxicological dynamics, immune recognition, protein corona formation, cytotoxicity, and genotoxic pathways; it also examines the endocytosis pathways through which MSNs are internalised and how particle charge and geometry dictate them, supported by in vivo findings. Finally, the review evaluates the emerging role of computational approaches, including molecular docking and dynamics simulations of inflammasome-associated proteins in elucidating the molecular mechanisms underlying MSN-induced toxicity, an area where direct experimental characterisation remains limited.