Fluorescent Silica Nanoparticles with Multivalent Inhibitory Effects towards Carbonic Anhydrases

Multifunctional silica nanoparticles decorated with fluorescent and sulfonamide carbonic anhydrase (CA) inhibitors were prepared and investigated as multivalent enzyme inhibitors against the cytosolic isoforms hCAI and II and the transmembrane tumor-associated ones hCAIX and XII. Excellent inhibitory effects were observed with these nanoparticles, with K-I values in the low nanomolar range (6.2-0.67nM) against all tested isozymes. A significant multivalency effect was seen for the inhibition of the monomeric enzymes hCAI and II compared to the dimeric hCAIX and hCAXII isoforms, where no multivalent effect was observed, suggesting that the multivalent binding is occurring through enzyme clustering.