Quantum Dot Based Luminescent Nanoprobes for Sigma‑2 Receptor Imaging

The increasing importance of sigma-2
receptor as target for the
diagnosis and therapy of tumors paves the way for the development
of innovative optically traceable fluorescent probes as tumor cell
contrast and therapeutic agents. Here, a novel hybrid organic–inorganic
nanostructure is developed by combining the superior fluorescent properties
of inorganic quantum dots (QDs), coated with a hydrophilic silica
shell (QD@SiO2 NPs), the versatility of the silica shell,
and the high selectivity for sigma-2 receptor of the two synthetic
ligands, namely, the 6-[(6-aminohexyl)­oxy]-2-(3-(6,7-dimethoxy-3,4-dihydroisoquinolin-2­(1H)-yl)­propyl)-3,4-dihydroisoquinolin-1­(2H)-one (MLP66) and 6-[1-[3-(4-cyclohexylpiperazin-1-yl)­propyl]-1,2,3,4-tetrahydronaphthalen-5-yloxy]­hexylamine
(TA6). The proposed nanostructures represent a challenging alternative
to all previously studied organic small fluorescent molecules, based
on the same sigma-2 receptor affinity moieties. Flow cytometry and
confocal fluorescence microscopy experiments, respectively, on fixed
and living cancerous MCF7 cells, which overexpress the sigma-2 receptor,
prove the ability of functionalized (QD@SiO2-TA6 and QD@SiO2-MLP66) NPs to be internalized and demonstrate their affinity
to the sigma-2 receptor, ultimately validating the targeting properties
conveyed to the NPs by sigma-2 ligand conjugation. The presented QD-based
nanoprobes possess a great potential as in vitro selective
sigma-2 receptor imaging agent and, consequently, could provide a
significant impact to future theranostic applications.