Controlling Growth of Ultrasmall Sub-10 nm Fluorescent Mesoporous Silica Nanoparticles

摘要

Mesoporous silica nanoparticles (MSNs) have recently attracted a lot of interest for future nanotheranostic applications because of their large surface-area and high biocompatibility. However, studies to date of MSNs are confined to >10 nm particle sizes which may result in unfavorable biodistribution characteristics for in vivo experiments and hence limit their clinical applications. Here we provide a full account of a synthesis approach to ultrasmall sub-10 nm mesoporous silica nanoparticles with narrow size distributions and homogeneous porous particle morphology. Key features enabling this structure control are (i) fast hydrolysis, (ii) slow condensation, and (iii) capping of particle growth by addition of a PEG-silane at different time-points of the synthesis. Variation of synthesis conditions including monomer/catalyst concentrations, temperature, and time-point of PEG-silane addition leads to synthesis condition-particle structure correlations as mapped out by a combination of results from data analysis of dynamic light scattering (DLS) and transmission electron microscopy (TEM) measurements. Results establish precise control over average particle diameter from 6 to 15 nm with increments below 1 nm. Solid state nuclear magnetic resonance (NMR) measurements, zeta-potential measurements, and thermogravimetric analysis (TGA) were conducted to reveal details of the particle surface structure. Long-term particle stability tests in deionized (Dl) water and phosphate buffered saline (PBS) IX buffer solution were performed using DLS demonstrating that the PEGylated particles are stable in physiological environments for months. Fluorescent single pore silica nanoparticles (mC dots) encapsulating blue (DEAC) and green (TMR) dyes were synthesized and characterized by a combination of DLS, TEM, static optical spectroscopy, and fluorescence correlation spectroscopy (FCS) establishing probes for multicolor fluorescence imaging applications. The ultraprecise particle size control demonstrated here in particular for sizes around and below 10 nm may render these particles an interesting subject for further fundamental studies of porous silica particle formation mechanisms as well as for sensing, drug delivery, and theranostic applications.