Paramagnetic, Silicon Quantum Dots for Magnetic Resonance and Two-Photon Imaging of Macrophages

Abstract

Quantum dots (QDs) are an attractive platform for building multimodality imaging probes, but the toxicity for typical cadmium QDs limits enthusiasm for their clinical use. Nontoxic, silicon QDs are more promising but tend to require short-wavelength excitations which are subject to tissue scattering and autofluorescence artifacts. Herein, we report the synthesis of paramagnetic, manganese-doped, silicon QDs (Si_(Mn) QDs) and demonstrate that they are detectable by both MRI and near-infrared excited, two-photon imaging. The Si_(Mn) QDs are coated with dextran sulfate to target them to scavenger receptors on macrophages, a biomarker of vulnerable plaques. TEM images show that isolated QDs have an average core diameter of 4.3 ± 1.0 nm and the hydrodynamic diameters of coated nanoparticles range from 8.3 to 43 nm measured by dynamic light scattering (DLS). The Si_(Mn) QDs have an r_1 relaxivity of 25.50 ± 1.44 mM^(−1) s^(−1) and an r_2 relaxivity of 89.01 ± 3.26 mM^(−1) s^(−1 )(37 °C, 1.4 T). They emit strong fluorescence at 441 nm with a quantum yield of 8.1% in water. Cell studies show that the probes specifically accumulate in macrophages by a receptor-mediated process, are nontoxic to mammalian cells, and produce distinct contrast in both T_1-weighted magnetic resonance and single- or two-photon excitation fluorescence images. These QDs have promising diagnostic potential as high macrophage density is associated with atherosclerotic plaques vulnerable to rupture.