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.

Next-generation in vivo optical imaging with short-wave infrared quantum dots.

For in vivo imaging, the short-wavelength infrared region (SWIR; 1000-2000 nm) provides several advantages over the visible and near-infrared regions: general lack of autofluorescence, low light absorption by blood and tissue, and reduced scattering. However, the lack of versatile and functional SWIR emitters has prevented the general adoption of SWIR imaging by the biomedical research community. Here, we introduce a class of high-quality SWIR-emissive indium-arsenide-based quantum dots (QDs) that are readily modifiable for various functional imaging applications, and that exhibit narrow and size-tunable emission and a dramatically higher emission quantum yield than previously described SWIR probes. To demonstrate the unprecedented combination of deep penetration, high spatial resolution, multicolor imaging and fast-acquisition-speed afforded by the SWIR QDs, we quantified, in mice, the metabolic turnover rates of lipoproteins in several organs simultaneously and in real time as well as heartbeat and breathing rates in awake and unrestrained animals, and generated detailed three-dimensional quantitative flow maps of the mouse brain vasculature.

Shortwave Infrared in Vivo Imaging with Gold Nanoclusters.

The use of visible/NIR-emitting gold nanoclusters (Au NCs), previously proposed for in vivo imaging, has been limited to some extent by low quantum yields (QYs) and the limited penetration of visible light in tissue. Here we report short wavelength infrared (SWIR, λ = 1-2 µm) emitting Au NCs with a good photoluminescence QY for this wavelength range (0.6% to 3.8% for λem = 1000 to 900 nm) and excellent stability under physiological conditions. We show that surface ligand chemistry is critical to achieving these properties. We demonstrate the potential of these SWIR-emitting Au NCs for in vivo imaging in mice. The Au NCs have a hydrodynamic diameter that is small (∼5 nm) enough that they exhibit a rapid renal clearance, and images taken in the SWIR region show better resolution of the blood vessels than in the NIR region.

Exceedingly small iron oxide nanoparticles as positive MRI contrast agents.

Medical imaging is routine in the diagnosis and staging of a wide range of medical conditions. In particular, magnetic resonance imaging (MRI) is critical for visualizing soft tissue and organs, with over 60 million MRI procedures performed each year worldwide. About one-third of these procedures are contrast-enhanced MRI, and gadolinium-based contrast agents (GBCAs) are the mainstream MRI contrast agents used in the clinic. GBCAs have shown efficacy and are safe to use with most patients; however, some GBCAs have a small risk of adverse effects, including nephrogenic systemic fibrosis (NSF), the untreatable condition recently linked to gadolinium (Gd) exposure during MRI with contrast. In addition, Gd deposition in the human brain has been reported following contrast, and this is now under investigation by the US Food and Drug Administration (FDA). To address a perceived need for a Gd-free contrast agent with pharmacokinetic and imaging properties comparable to GBCAs, we have designed and developed zwitterion-coated exceedingly small superparamagnetic iron oxide nanoparticles (ZES-SPIONs) consisting of ∼3-nm inorganic cores and ∼1-nm ultrathin hydrophilic shell. These ZES-SPIONs are free of Gd and show a high T1 contrast power. We demonstrate the potential of ZES-SPIONs in preclinical MRI and magnetic resonance angiography.