Facile Synthesis of Gd–Cu–In–S/ZnS Bimodal Quantum Dots with Optimized Properties for Tumor Targeted Fluorescence/MR <i>In Vivo</i> Imaging

Dual-modal imaging techniques have gained intense attention for their potential role in the dawning era of tumor early accurate diagnosis. Chelate-free robust dual-modal imaging nanoprobes with high efficiency and low toxicity are of essential importance for tumor targeted dual-modal <i>in vivo</i> imaging. It is still a crucial issue to endow Cd-free dual-modal nanoprobes with bright fluorescence as well as high relaxivity. Herein, a facile synthetic strategy was developed to prepare Gd-doped CuInS/ZnS bimodal quantum dots (GCIS/ZnS, BQDs) with optimized properties. The fluorescent properties of the GCIS/ZnS BQDs can be thoroughly optimized by varying reaction temperature, aging time, and ZnS coating. The amount of Gd precursor can be well-controlled to realize the optimized balance between the MR relaxivity and optical properties. The obtained hydrophobic GCIS/ZnS BQDs were surface engineered into aqueous phase with PEGylated dextran-stearyl acid polymeric lipid vesicles (PEG-DS PLVs). Upon the phase transfer, the hydrophilic GCIS/ZnS@PLVs exhibited pronounced near-infrared fluorescence as well as high longitudinal relaxivity (<i>r</i>₁ = 9.45 mM^–1 S^–1) in water with good colloidal stability. <i>In vivo</i> tumor-bearing animal experiments further verified GCIS/ZnS@PLVs could achieve tumor-targeted MR/fluorescence dual-modal imaging. No toxicity was observed in the <i>in vivo</i> and <i>ex vivo</i> experiments. The GCIS/ZnS@PLVs present great potential as bimodal imaging contrast agents for tumor diagnosis