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 CuInS 2/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.
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