Hollow mesoporous silica nanoparticles with tunable shell thickness and pore size distribution for application as broad-ranging pH nanosensor

Ratiometric fluorescence pH sensor is widely used in measuring intracellular pH but the pH sensing range is commonly limited in the range of pK_a ± 1 of the pH sensitive dye. In previous work, we demonstrated that the pK_a value of the pH sensitive dye and the pH sensing range of a nanosensor can be extended by varying the curvature of the silica surface which the dye is affixed on. Based on this idea, a powerful pH sensor with a pH sensing range more than 5 units is possible. In the present paper, we synthesized hollow mesoporous silica nanoparticles (HMSNs) from an oil-in-water microemulsion system. Both the shell thickness and pore size distribution could be tuned simultaneously by altering the organic solvents used to dissolve hydrophobic components. Furthermore, small and uniform nanoparticles (less than 100 nm) were obtained through a kinetic control that is beneficial for intracellular studies. Finally, we took advantage of the broad pore size distribution of as-synthesized HMSNs, and loaded a pH sensitive dye and a reference dye onto the surface to fabricate pH sensors with a very large pH measuring range of 3.2-9.0 in a ratiometric fluorescence method.