Glutathione-coated PbS quantum dots with tunable emission were synthesized in the aqueous phase and used for non-invasive tissue imaging in the second near-infrared biological window.

Near-infrared (NIR) fluorescence imaging at wavelengths from 1000 to 1500 nm (2nd-NIR window) is a promising modality for in vivo fluorescence imaging because of the deeper tissue penetration with lower tissue scattering of the 2nd-NIR light. For such in vivo fluorescence imaging, highly fluorescent probes in the 2nd-NIR wavelength region are needed. Although single-walled carbon nanotubes and Ag₂S quantum dots (QDs) have recently appeared as 2nd-NIR fluorescent probes, their fluorescence brightness is relatively low (quantum yields <6%). In this study, we developed a synthetic method for preparing highly fluorescent PbS/CdS core–shell QDs (quantum yields, 17% in water) with narrow band widths (<200 nm) that emit in the 2nd-NIR region. By overcoating of a CdS shell onto a PbS QD core, we could easily control the emission wavelengths of the PbS/CdS QDs at 1000 to 1500 nm. To use the QDs for in vivo imaging, we investigated the optical properties of QDs (penetration depth and blurring of fluorescence images in slices of skin, brain, and heart in mice) in the 2nd-NIR region. We found that the 2nd-NIR fluorescence imaging at ca.1300 nm using the PbS/CdS QDs results in the highest signal to background ratio with a low blurring for in vivo imaging. To confirm the capabilities of the PbS/CdS QDs for in vivo imaging, we conducted fluorescence angiography imaging of a mouse head.

We report a one-step synthetic strategy for the preparation of recombinant protein (EGFP-Protein G)-coated PbS quantum dots for dual (visible and second-NIR) fluorescence imaging of breast tumors.

Near-infrared (NIR) fluorescent imaging is a powerful tool for the non-invasive visualization of the inner structure of living organisms. Recently, NIR fluorescence imaging at 1000–1400 nm (second optical window) has been shown to offer better spatial resolution compared with conventional NIR fluorescence imaging at 700–900 nm (first optical window). Here we report lead sulfide (PbS) quantum dots (QDs) and their use for in vivo NIR fluorescence imaging of cerebral venous thrombosis in septic mice. Highly fluorescent PbS QDs with a 1100 nm emission peak (QD1100) were prepared from lead acetate and hexamethyldisilathiane, and the surface of QD1100 was coated with mercaptoundecanoic acid so as to be soluble in water. NIR fluorescence imaging of the cerebral vessels of living mice was performed after intravascular injection (200–300 μL) of QD1100 (3 μM) from a caudal vein. By detecting the NIR fluorescence of QD1100, we achieved non-invasive NIR fluorescence imaging of cerebral blood vessels through the scalp and skull. We also achieved NIR fluorescence imaging of cerebral venous thrombosis in septic mice induced by the administration of lipopolysaccharide (LPS). From the NIR fluorescence imaging, we found that the number of thrombi in septic mice was significantly increased by the administration of LPS. The formation of thrombi in cerebral blood vessels in septic mice was confirmed by enzyme-linked immunosorbent assay (ELISA). We also found that the number of thrombi significantly decreased after the administration of heparin, an inhibitor of blood coagulation. These results show that NIR fluorescence imaging with QD1100 is useful for the evaluation of the pathological state of cerebral blood vessels in septic mice.

Indocyanine green (ICG) is the only near-infrared (NIR) fluorescent dye which is approved for medical applications. However, ICG has several drawbacks such as aqueous instability, photodegradation, and low fluorescence quantum yield (2.5% in water), which lead to the limitation on the use of ICG for in vitro and in vivo NIR fluorescence imaging. Free ICG rapidly aggregates in physiological buffer solutions, and its fluorescence diminishes within several days. The objective of this work is to provide an easy method for the enhancement of the stability and fluorescence brightness of ICG in aqueous solutions for NIR fluorescence imaging. Herein, we report that the incorporation of ICG into small calix[4]arene (S4-6) micelles (<5 nm in diameter) significantly improves the aqueous stability and fluorescence brightness of ICG. The fluorescence quantum yields of ICG-calix[4]arene micelles are increased up to ∼6% in aqueous solutions. Using the ICG-calix[4]arene micelles, we achieved non-invasive NIR fluorescence imaging of the liver and lymph system in mice. Furthermore, we achieved NIR fluorescence imaging of nude mice bearing human breast tumors using an ICG conjugated antibody which is incorporated into the calix[4]arene micelles. Preparation of the calix[4]arene micelles including ICG is very easy and the micelle system does not show significant cytotoxicity. The ICG-calix[4]arene micelle system acts as a highly stable and bright probe for in vitro and in vivo NIR fluorescence imaging.