Design of Dendritic Large-Pore Mesoporous Silica Nanoparticles with Controlled Structure and Formation Mechanism in Dual-Templating Strategy.

Dendritic large-pore mesoporous silica nanoparticles (DLMSN) is an important biodegradable drug carrier due to its high porosity, which can be prepared by coassembly of a major template and an auxiliary template in aqueous solution, followed by hydrolysis of tetraethyl orthosilicate (TEOS). The auxiliary template is key to obtaining dendritic large-pore structures; however, how to choose the auxiliary template to obtain the desired pore structure is largely unknown. This is because the formation mechanism of DLMSN is still not clear. In this study, a series of therapeutic agent molecules were used as the auxiliary templates to study the control of the pore morphology of DLMSN. Transmission electron microscopy observation and theoretical modeling were used to study the micelle formation, and early stage silica formation was also observed. It is proposed that the silica branches and sheets formed by hydrolysis of TEOS on single micelle and micelle bundles, which formed the initial nanoparticles with spherical structures and new silica species growing on the early formed particles to form DLMSN. The fine control of pore morphology was demonstrated by using auxiliary templates with different structural characteristics, which were used for selective drug loading. This work provides a design strategy of how to choose suitable auxiliary templates for preparing DLMSN with desired pore structure for biomedical applications.