PEOLATED SILICA NANOCAPSULES VIA BIOINSPIRED SILIFICATION FOR CELLULAR IMAGING

Abstract

In this study, a bioinspired silification strategy has been successfully developed to synthesize PEOlated silica nanocapsules at room temperature and near-neutral pH environment by using PEO-based block copolymer micelles as templates, mimicking the process of silica skeleton formation of marine organisms. The success of this approach lies on the encapsulation of the silica precursors in the core of the polymeric micelles, which results in the confinement of the silica shell formation at the interface between the core and corona of the polymeric micelles. Such strategy allows the synthesized silica nanocapsules to be intrinsically covered by a layer of free PEO chains that enable them to exhibit excellent colloidal stability in aqueous environment.

On top of being used for formation of pure silica nanocapsules, the bioinspired silification is also employed as a general platform for synthesis of functional silica nanocapsules by encapsulating functional hydrophobic compounds in the core of the silica nanocapsules. For example, superparamagnetic silica nanocapsules have been prepared by encapsulating hydrophobic iron oxide nanocrystals inside the core of the silica nanocapsules, forming PEOlated Fe3O4@SiO2 nanoparticles. The silica shell formation did not cause any detrimental effect on the encapsulated iron oxide nanocrystals with respect to their size, morphology, crystallinity, and magnetic properties, clearly demonstrating the benign characteristics of the bioinspired silification approach. These superparamagnetic silica nanocapsules are demonstrated to exhibit excellent colloidal stability and thus an excellent candidate as magnetic resonance imaging (MRI) contrast agent. In addition to iron oxide nanocrystals, fluorescent conjugated polymers have been successfully loaded into the core of the silica nanocapsules. The fluorescent silica nanocapsules are shown to exhibit large absorption coefficient and high quantum yield, which suggest that they possess the required brightness for fluorescence cellular imaging. Indeed, upon incubation with breast cancer cells, the fluorescent silica nanocapsules were internalized by the cells, which can then be visualized by using confocal laser scanning microscopy. Moreover, by conjugating folic acid on the surface of the fluorescent silica nanocapsules, targeted imaging of the breast cancer cells is demonstrated, indicating their potentials as probes for early cancer detection.

Finally, the bioinspired silification has been employed to integrate the fluorescence of conjugated polymers and superparamagnetism of iron oxide nanocrystals inside the silica nanocapsules, forming a new class of bi-functional magnetic silica nanocapsules. The synthesized bi-functional silica nanocapsules are shown to exhibit the desired dual functionality of fluorescence and superparamagnetism in a single entity, which make them potentially to be used as dual mode cellular imaging contrast agent. The applicability of the bi-functional silica in cellular imaging was studied by incubating them with human liver cancer cells, the result of which demonstrated that the cells could be visualized via dual mode of fluorescence and magnetic resonance imaging. Furthermore, the superparamagnetic behavior of the bi-functional silica nanocapsules was successfully exploited for in vitro magnetic guided delivery of the nanocapsules into the cancer cells, thereby highlighting their potentials for targeting biomedical applications.