Defect Engineering of Mesoporous Silica Nanoparticles for Biomedical Applications

ConspectusThe goddess Venus has been known for her armless beauty. Such a unique artistic effect teaches us that the imperfection in one aspect may result in a great aesthetics in another aspect. The existence of structural defects in nanomaterials (substitutional impurities and vacancies) endows them with diverse and fascinating physicochemical properties, such as optical properties and redox reaction capabilities. Therefore, defect engineering of controllably regulating the types and concentrations of defects in nanoparticles has been paid great attention in nanosynthetic chemistry for tailoring the performances of nanomaterials for diversified practical applications, such as biomedical applications.Mesoporous silica nanoparticles (MSNs) have been extensively applied as nanocarriers in biomedicine, due to their well-defined pore structure and particle morphology, extraordinarily large specific surface area and pore volume, tunable pore size, and framework composition. These nanoparticles have been considered as promising candidates for application in multiple therapeutic or diagnostic applications, by acting as drug carriers or supports for functional materials. The synthesis of MSN is usually based on sol–gel chemistry according to a bottom-up approach in a hydrothermal environment, where the silica precursor tetraethoxysilane molecules condense with each other and −Si–O–Si– bonds form consequently, under the assistance of surfactants as structural-directing agents, finally resulting in the formation of a mesoporous nanostructure. Accompanying the pore structure evolution, which has been being the major focus in the MSNs synthesis and application in the past decades, alternatively, the composition of MSN framework can also be elaborately engineered for the material functionalization and the application broadenings of MSNs, facilely by properly regulating the experimental conditions and reactants. Especially, the defect engineering of MSNs has been extensively explored very recently for broadening biomedical applications of these nanocarriers.In the last several years, our laboratory has developed three general strategies to engineer various functional chemical constituents in the MSN framework as structural defects, conferring the nanocarriers with multiple additional functions: (1) doping metal element M (M = Fe, Cu, Mn, Mg, Ca) in silica to form a −Si–O–M– metal silicate hybrid framework; (2) hybridizing organic group R (R = thioether, ethane, phenylene) in silica to fabricate a −Si–R–Si– molecularly organic–inorganic hybrid framework; (3) creating oxygen vacancies in silica by forming an oxygen-deficient framework abundant with −Si–Si– bonds. These material-engineering approaches have led to the generation of numbers of structural defects in the pristine silsesquioxane framework of MSNs, making these "defective nanoparticles" capable of presenting various unique physicochemical properties benefiting biomedical applications, such as triggered biodegradability for controlled drug release; catalytic performance for triggering in vivo chemical reactions generating therapeutic effects; paramagnetism for enabling magnetic resonance imaging; luminescent property for cell imaging, etc. In this Account, we will provide a concise and concentrated summary on the advances in the preparation of defective MSNs mainly in our laboratory, as well as the therapeutic and diagnostic applications of these versatile nanosystems, hoping to provide more inspirations to future nanomedicine design.