Gadolinium-Based CuInS₂/ZnS Nanoprobe for Dual-Modality Magnetic Resonance/Optical Imaging

Abstract

A new magnetic resonance/optical nanoprobe with specific cellular targeting capabilities based on nontoxic CuInS2/ZnS quantum dots (QDs) with direct covalent attachment of a Gd(III)-complex for tumor-specific imaging is reported. We introduce amphiphilic poly(maleic anhydride-alt-1-octadecene) to interdigitate with hydrophobic, protective agents on the surface of CuInS2/ZnS QDs that allows phase transfer of hydrophobic QDs from the organic into aqueous phase. Carbodiimide chemistry is used to covalently couple the Gd(III) complex on the surface of CuInS2/ZnS QDs, and then folic acid is further utilized to functionalize this dual-modality nanoprobe for active tumor targeting based on the fact that the membrane-associated folate receptor is overexpressed in many tumor cells. The longitudinal relaxivity value is 3.72 mM(-1) s(-1) for the dual-modality nanoprobe and a clear, positive, and increasing contrast enhancement of magnetic resonance signals concurrently with increasing Gd(III) concentration is observed. The dual-modality nanoprobe exhibits negligible cytotoxicity with >80% cell viability at a concentration of up to 100 μg/mL in human cervical (HeLa), human liver carcinoma (HepG2), and human breast (MCF-7) cells after 24 h. The specificity of folic-acid-conjugated nanoprobe cellular uptake has been investigated by confocal scanning laser imaging, which revealed that HeLa cells, expressing the folate receptor, internalized a higher level of dual-modality nanoprobes than HepG2 and MCF-7 cells.

Magnetically Engineered Semiconductor Quantum Dots as Multimodal Imaging Probes

“…These values were 6 and 14 times higher than for free Gd‐DOTA, ascribed to the lower tumbling rate of the Gd‐chelates attached to a hydrophilic silica surface. In the absence of silica coating, Gd ions can be attached at the surface of QDs by either an amidation coupling reaction between Gd‐chelating ligands and the surface capping ligands of QDs such as CdSeTe@CdS, CdTe@ZnS, CdS, and CuInS 2 @ZnS, or utilizing mono‐, di‐ or multi‐dentate thiol‐containing Gd‐chelating ligands directly coordinating with the surface cations of QDs as demonstrated for InP@ZnS (Figure c) and CdSe@ZnS QDs. Nevertheless, the high binding affinity of the chelating ligand may heavily etch the QDs before it coordinates with the paramagnetic metal ions for forming the magnetic metal chelates on the QD surface.…”

Advances in targeting the folate receptor in the treatment/imaging of cancers

“…The benefits of using folic acid in this way are manifold: it is non-immunogenic, cost efficient, has high stability and tissue permeability, possesses a low molecular weight and can be easily conjugated to diverse types of organic molecules, antibodies and nanoparticles. 30 There are only certain identified positions on the folic acid core scaffold where it can be attached to the rest of the conjugate without compromising the high binding strength to FRα, with one position proving to be the most favoured ( Fig. 2 ).…”

Nanoparticles speckled by ready-to-conjugate lanthanide complexes for multimodal imaging

“…[1][2][3][4][5] Fluorescent and paramagnetic materials for the construction of multimodal NPs are routinely recruited from among visible/NIR dyes, [6][7][8][9][10][11][12][13][14][15] semiconductor quantum dots (QDs), [16][17][18][19][20][21][22][23][24][25][26] upconversion NPs (UCNPs), [27][28][29] carbon NPs, 30,31 noble metal QCs, [32][33][34][35] lanthanide ions, 31,32 SPION, [11][12][13][14]24,25,32 oxides [36][37][38][39] or vanadates 40,41 of gadolinium, and coordination complexes of lanthanides. With the infiltration of molecular and nanomaterials contrast agents into the clinical settings, the quality and precision of biomedical...…”

“…For example, stable contrast agents for MRI and fluorescence imaging are prepared by the conjugation of Gd(III) complexes to organic dyes such as porphyrin, 6,7 fluorescein 8 and Cy5.5; 9,10 QDs such as CuInS 2 / ZnS, 17,18 silicon, 19 InP, 20 CdSeTe/CdS, 21 CdSe/ZnS 22 and CdTe/ ZnS; 23 and persistent luminescence NPs, 54 UCNP, [27][28][29] and gold QCs. For example, stable contrast agents for MRI and fluorescence imaging are prepared by the conjugation of Gd(III) complexes to organic dyes such as porphyrin, 6,7 fluorescein 8 and Cy5.5; 9,10 QDs such as CuInS 2 / ZnS, 17,18 silicon, 19 InP, 20 CdSeTe/CdS, 21 CdSe/ZnS 22 and CdTe/ ZnS; 23 and persistent luminescence NPs, 54 UCNP, [27][28][29] and gold QCs.…”