Microgel bioconjugates for targeted delivery to cancer cells
Blackburn, William H.
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The use of hydrogel nanoparticles, or nanogels, as targeted delivery vehicles to cancer cells was described. The nanogels were synthesized by free radical precipitation polymerization, with poly(N-isopropylmethacrylamide) as the main monomer, and have a core/shell architecture. The nanogels were near 50 nm in radius, contained fluorescein for visualization, and had an amine-containing shell for bioconjugation, making these particles ideal for delivery studies. The nanogels were conjugated with the YSA (YSAYPDSVPMMSC) peptide, which is an ephrin mimic, allowing for uptake by the EphA2 (erythropoietin-producing hepatocellular) receptor. We have delivered YSA-conjugated nanogels to Hey cells and BG-1 cells, as evidenced by fluorescence microscopy. We have shown that the nanogels can encapsulate siGLO Red Transfection Indicator (siGLO) and deliver the siGLO to Hey cells in vitro. After successful delivery of the non-targeting siGLO, we delivered siRNA for knockdown of epidermal growth factor receptor (EGFR). We have shown protein knockdown from 24-120 h after nanogel delivery, as well as knockdown with different siRNA concentrations delivered to the cells. Furthermore, addition of taxol following EGFR knockdown suggests that the chemosensitivity of the Hey cells is increased. Successful in vitro delivery of the nanogels prompted in vivo studies with the nanogels. The nanogels were used to encapsulate silver nanoclusters for potential bioimaging applications. Targeting of the nanogels to MatrigelTM plugs in mice suggest that the particles hold promise as in vivo delivery agents.