Mesoporous silica (MS) nanoparticles (NPs) are attracting much attention of late due to their unique characteristics, including size control, large internal surface area, and easy surface modification, making them promising candidates for biomedical applications. However, the low particle stability, nonspecific biomolecule adsorption, and unintentional degradation of these porous silica NPs in biological media result in rapid unintentional uptake by the immune system and limit their potential for in vivo biological use. Recently, we have shown that MS NPs have lower hemolytic activity and cytotoxicity than their nonporous counterparts.[1,2,3] Additionally, we found that small MS NPs (<50 nm) with polyethylene glycol (PEG) modification and hydrothermal treatment are shown to exhibit higher particle stability in biological media at 37 oC compared to bare MS NPs and PEGylated MS NPs without hydrothermal treatment. These hydrothermally treated PEGylated particles are highly biocompatiable, resistant to degradation and nonspecific protein adsorption, and less efficiently taken up by macrophages.[4] Herein, we incorporate a secondary hydrophobic silane (chlorotrimethyl silane or 3,3,3-trifluoropropylchlorodimethyl silane) into PEGylated MS NPs to further increase the long-term particle stability in simulated body fluid, compared to hydrothermally treated PEGylated MS NPs. In addition, these co-modified MS NPs can be dried and redispersed in biological media and still maintain their long-term particle stability in physiological conditions. To demonstrate the versatility of this co-modified method, we further demonstrate the redispersity of ultrasmall (<30 nm), fluorescent and magnetic co-modified MS NPs. In addition, doxorubicin is used to study the redispersity, loading capacity and delivery kinetics of the co-modified MS NPs. Finally, these redispersible drug-loaded MS NPs show dose-dependent cytotoxic effect to cancerous cells (HeLa) and exhibit higher cytotoxicity than free hydrophobic anticancer drugs.

Ultrastable, redispersible, and small organically modified mesoporous silica nanoparticles

244th National Meeting (2012)

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