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Biofunctionalized phospholipid-capped mesoporous silica nanoshuttles for targeted drug delivery: improved water suspensibility and decreased nonspecific protein binding.

A main challenge in nanobiomedicine is the engineering of nanostructures or nanomaterials that can efficiently encapsulate drugs at high load, cross cell membranes, and controllably release their cargo at target sites. Although mesoporous silica nanoparticles (MSNs) are safe, versatile, and promising carrier materials for targeted drug delivery, their aggregation phenomena under physiological conditions (or salt-containing environments) and their nonspecific binding in protein-containing solutions (or serum) limit their applications in biological science and biomedicine. To address this challenge, we have developed a novel delivery system, termed a nanoshuttle, comprising a nanoscale PEGylated-phospholipid coating and 13-(chlorodimethylsilylmethyl)heptacosane-derivatized MSNs, in which therapeutic or imaging agents may be trapped and ligand-assisted targeted delivery may be achieved through surface functionalization of the phospholipids. As a proof of concept in this study, we selected fluorescein isothiocyanate and folate as the imaging tracer and targeted ligand, respectively. Relative to the bare MSNs, the lipid-capped MSNs exhibited superior suspensibility in phosphate-buffered saline and much lower nonspecific binding in vitro. Furthermore, enhanced specific cellular uptake by Hela cells occurred after administering the folate-sensitized phospholipid-capped MSNs. Our results suggest that these highly versatile multifunctional MSNs are promising vectors for nanomedicine applications.