Multiplexed In Vivo Imaging Using Size‐Controlled Quantum Dots in the Second Near‐Infrared Window

Abstract

PbS/CdS core/shell quantum dots (QDs) that emit at the second near‐infrared (NIR‐II, 1000–1700 nm) window are synthesized. The PbS seed size and CdS shell thicknesses are carefully controlled to produce bright and narrow fluorescence that are suitable for multiplexing. A polymer encapsulation yields polymer‐encapsulated NIR‐II QDs (PQDs), which provides the QDs with long‐term fluorescence stability over a week in biological media. Exploiting the simple bioconjugation capability of PQDs, folic acids are conjugated to PQDs that can efficiently label folate receptor overexpressing cell lines. The PQDs afford multiplexed and nearly real‐time longitudinal whole‐body in vivo imaging. Two NIR‐II QD probes are prepared: folic acid‐conjugated PQDs (FA‐PQDs) emitting at 1280 nm and unconjugated PQDs emitting at 1080 nm. The two PQDs are engineered to have compact and similar hydrodynamic sizes. A mixture of the folic acid‐conjugated PQD and unconjugated PQDs is injected intravenously into a tumor‐xenografted mouse, and the signals from them are monitored. This NIR‐II whole‐body imaging with the two PQDs provides precise evaluation of the active ligand‐assisted tumor‐targeting capability of the FA‐PQD probe because the hydrodynamic size control of the two PQDs effectively eliminates effects from the size‐dependent accumulations by permeations and retentions in tumors.

Nanotechnology for cardiovascular diseases

“…The emergence and development of new technologies have led to novel fluorescent nanoparticles emitting in the second NIR window (NIR-II, 1,000–1,700 nm), which allows NIRF imaging to visualize deep tissues with an unprecedented degree of clarity for diagnosis or surgical guidance. 100 , 101 , 102 , 103 Some novel biofunctionalized NIR-II nanoparticles, such as quantum dots (QDs), 56 , 104 , 105 single-walled carbon nanotubes (SWNTs), 106 , 107 and rare earth-based upconversion nanoparticles (UCNPs), 108 , 109 , 110 have been reported for the in vivo imaging of atherosclerosis or AMI, which will help to expedite the clinical transition of NIR imaging. Although differentiating vulnerable plaques from stable plaques remains challenging in the clinic, Gao et al.…”

Recent Advances in Metal Chalcogenide Quantum Dots: From Material Design to Biomedical Applications

“…The researchers synthesized probes with 1080 and 1280 nm emission from 4.2 and 5.1 nm PbS seeds, demonstrating the feasibility of emission spectral tuning through size control. [70] Liu et al reported trialkylphosphine-controlled growth of Ag 2 Te QDs and achieved emission wavelength from 950 to 2100 nm. [50] It is because the coordination between trialkylphosphine and the Ag ion is stronger than that of 1-octanethiol, and thus the precise size control of Ag 2 Te QDs can be achieved.…”

Fluorescence Imaging in Second Near‐infrared Window: Developments, Challenges, and Opportunities

“…Multiplexed bioimaging enables the simultaneous analysis of multiple targets and thus has strong potential for applications in real‐time observation of living biological and physiological processes and in clinical practice for noninvasive diagnostics, image‐guided surgery, etc. Kim et al [ 85 ] fabricated bright and narrow PbS/CdS QDs with different emission wavelengths by adjusting the size and accurately evaluated the active ligand‐assisted tumor targeting ability and passive tumor accumulation effect by two‐color imaging. Chen et al [ 27 ] used dual probes, IR‐FD, and PbS QDs for dual‐color imaging in NIR‐IIa and NIR‐IIb, enabling high‐precision observation of micrometastases in lymph nodes.…”