Macrophage-Targeted Quantum Dots with Short-Wave Infrared Emission for In Vivo Breast Cancer Imaging

Abstract In vivo characterization and visualization of tumors often relies on radioactive tracers and expensive, complex equipment, which limits the frequency of analysis, throughput, and accessibility. Short-wave infrared (SWIR) fluorescence is a new nonradioisotopic imaging modality with flexible readouts at high depth and high signal-to-background contrast. Here, we report semiconductor quantum dots (QDs) with SWIR fluorescence engineered to selectively target tumor-associated macrophages (TAMs) by functionalization with the polysaccharide dextran (Dex). TAMs are often abundant in the tumor microenvironment and mediate immune suppression, angiogenesis, metastatic progression, and therapy resistance, making them important targets for in situ analysis. We compare QD-Dex probes with QDs coated with polyethylene glycol (QD-PEG) as nontargeted controls with equivalent fluorescence, hydrodynamic size, and electrostatic charge. In vitro, QD-Dex exhibited receptor-mediated uptake by cultured macrophages whereas QD-PEG uptake was only through noncompetitive passive processes. In vivo, SWIR imaging of immunocompetent mice bearing TAM-rich orthotopic 4T1 mammary tumors revealed tumor retention of QD-Dex after intravenous administration. Tumor signals for QD-PEG were much lower in comparison. Tumor signals for QD-Dex exceeded blood levels ∼2 h after injection and decayed substantially after 24 h, providing an appropriate time window for preclinical imaging studies in rodents. These findings establish baseline metrics for macrophage-targeted SWIR nanoprobes as a platform for preclinical in vivo tumor analysis without ionizing radiation.