Glyco-Coated CdSe/ZnS Quantum Dots as Nanoprobes for Carbonic Anhydrase IX Imaging in Cancer Cells

Abstract

The bioimaging of cancer cells by the specific targeting of overexpressed biomarkers is an approach that holds great promise in the identification of selective diagnostic tools. Tumor-associated human carbonic anhydrase (hCA) isoforms IX and XII have been considered so far as well-defined biomarkers, with their expression correlating with cancer progression and aggressiveness. Therefore, the availability of highly performant fluorescent tools tailored for their targeting and able to efficiently visualize such key targets is in high demand. We report here on the design and synthesis of a kind of quantum dot (QD)-based fluorescent glyconanoprobe coated with a binary mixture of ligands, which, according to the structure of the terminal domains, impart specific property sets to the fluorescent probe. Specifically, monosaccharide residues ensured the dispersibility in the biological medium, CA inhibitor residues provided specific targeting of membrane-anchored hCA IX overexpressed on bladder cancer cells, and the quantum dots imparted the optical/fluorescence properties.

Green synthesis of glyco-CuInS2 QDs with visible/NIR dual emission for 3D multicellular tumor spheroid and in vivo imaging

“…In vivo near-infrared (NIR) fluorescence imaging of these glyco-QDs revealed the importance of the terminal sialic acid residues for achieving prolonged in vivo lifetime [ 14 ]. Recently, Richichi's group reported a kind of CdSe/ZnS QDs-based fluorescent glyconanoprobe as nanoprobes for carbonic anhydrase IX imaging in cancer cells [ 15 ]. However, to date, the majority of glyco-QDs related research in biomedicine focused on Cd-based QDs including CdS, CdSe, and CdTe QDs, which are often added by ZnS and/or ZnSe as protective shells.…”

High-Affinity NIR-Fluorescent Inhibitors for Tumor Imaging via Carbonic Anhydrase IX

“…Since the discovery of CAIX as a hypoxic tumor biomarker, − numerous studies have used antibodies, small-molecule compounds, and nanoparticles conjugated to fluorescent or radioactive elements designed both for tumor imaging and cancer treatment. − ,,,− Several small-molecule probes have reached clinical trials. For instance, 18 F-VM4-037, a small-molecule radiotracer developed on the sulfonamide pharmacophore, a derivative of the CA ligand ethoxzolamide, failed to localize the ccRCC tumor as it had a high background in the kidney and liver .…”

Atropo/Tropo Flexibility: A Tool for Design and Synthesis of Self-Adaptable Inhibitors of Carbonic Anhydrases and Their Antiproliferative Effect

“…Inhibitor and enzyme solutions were preincubated together for 15 min at room temperature prior to assay in order to allow for the formation of the E–I complex. The inhibition constants were obtained by nonlinear least-squares methods using PRISM 3 and the Cheng–Prusoff equation, as reported earlier ,,,,− and represent the mean from at least three different determinations. All CA isoforms were recombinant ones obtained in-house as reported earlier, − and their concentrations in the assay system ranged between 7.6 and 12.5 nM.…”