Monodisperse and Water-Soluble Quantum Dots for SWIR Imaging via Carboxylic Acid Copolymer Ligands

Compared to the visible and near-infrared, the short-wave infrared region (SWIR; 1000-2000 nm) has excellent properties for in vivo imaging: low autofluorescence, reduced scattering, and a low-absorption cross-section of blood or tissue. However, the general adoption of SWIR imaging in biomedical research will be enhanced by a broader availability of versatile and bright contrast materials. Quantum dots (QDs) are bright and compact SWIR emitters with narrow size distributions and emission spectra, but their use is limited by the shortcomings of established ligand systems for SWIR QDs. Established ligands often result in SWIR probes with either limited colloidal stability, large size, or broad size distribution or a combination of all three. We present a polymeric QD ligand designed to be compatible with oleate-coated QDs. Our polymeric acid ligand is a copolymer bearing carboxylic acid anchoring groups and PEG-550 chains to solubilize the QD-ligand construct. After a mild and rapid ligand exchange, the resulting constructs are compact (<11 nm hydrodynamic diameter) and have narrow size distribution. Both qualities are preserved for several months in isotonic saline. The constructs are bright in vivo, and to demonstrate their suitability for imaging, we perform whole-body imaging and lymphatic imaging, including visualization of lymphatic flow.