Clickable Multifunctional Large-Pore Mesoporous Silica Nanoparticles as Nanocarriers

Large-pore mesoporous silica nanoparticles (LP-MSNs) with defined particle size (<200 nm) are promising carrier systems for the cellular delivery of macromolecules. Ideal nanocarriers should be adaptable in their surface properties to optimize host–guest interactions; thus, surface functionalization of the nanovehicles is highly desirable. In this study, we synthesized various monofunctional LP-MSNs by incorporating different organic groups into the silica framework via a co-condensation approach. Further, we applied a delayed co-condensation strategy to create spatially segregated core–shell bifunctional LP-MSNs. Diverse particle morphologies were obtained by adding different organosilanes to the silica precursor solution. The effect of organosilanes in the co-condensation process on particle size and pore structure formation is also discussed. Surface functional groups were then used for binding stimuli-responsive linkers. These were finally exploited for copper-free click chemistry for cargo conjugation to create a delivery system with controlled cargo release. Model cargo release experiments in buffer using these new multifunctional LP-MSNs demonstrate their ability in controlled cargo uptake and release and their potential for biomolecule delivery.