Shell-by-shell synthesis of multi-shelled mesoporous silica nanospheres for optical imaging and drug delivery.

Self-templated synthesis involving interior channel wall protection as well as outermost surface passivation was crucial to successful synthesis of multi-shelled mesoporous silica nanospheres. The shell-by-shell fabrication of double- and triple-walled mesoporous silica nanospheres downsized to ∼100 nm. The multi-shelled mesoporous silica can be built as rattle-type or hollow structures with ∼110 nm of double-shelled and ∼140 nm of triple-shelled sizes. Notably, the shell-to-shell distance can be tuned by controlling the etching period from the self-templation processes without changing the multi-shelled size or interior core diameter. The multi-shelled mesoporous nanostructures provide a platform for the development of a multifunctional vector by the inclusion of functional species into shell-to-shell cavities and porous shells. The encapsulation of the fluorophore and drug in shell-to-shell space and mesoporous shells showed that multi-shelled silica spheres can be used in dual-modality for imaging and drug co-delivery vectors through the appropriate selection of pH-dependent molecules. The in vitro evaluation in triple-shelled silica indicated that an anti-cancer doxorubicin (DOX), loaded in the outer periphery space, was successfully carried and released in the cytoplasm, then entered nuclei while fluorescein FITC (primarily distributed in inner periphery space) was effectively encapsulated inside the spheres. The double- and triple-shelled nanospheres consistently provided imaging probes with visible tracking capability in vitro and in vivo.