A multistage delivery system based on biodegradable mesoporous silicon particles loaded with one or multiple second stage nano-particles is likely to be useful for drug delivery. Upon intravenous injection the silicon nano-carriers will travel through the blood stream and migrate to the vessel wall. Vascular endothelial cells have been shown to be promising candidates for drug delivery as they represent both an anchor point and target.[1] It has been shown that human endothelial cells can act as nonprofessional phagocytes internalizing our silicon micron-sized nano-carriers.[2] The complete understanding of the molecular mechanisms required for the internalization of the particles into cells, as well as their fate once internalized, is crucial for the choice and formulation of appropriate second stage particles to be loaded in the silicon carrier. For example, different types of coatings or functionalization for both silicon nano-carriers and nano-particles could favor different trafficking pathways or promote endosomal escape following cellular uptake. In this study the uptake and trafficking of silicon nano-carriers in Human Microvascular Vein Endothelia Cells (HMVECs) was monitored using TEM, confocal microscopy and immunofluorescence.

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