In vivo molecular imaging for immunotherapy using ultra-bright near-infrared-IIb rare-earth nanoparticles.
The near-infrared-IIb (NIR-IIb) (1,500-1,700nm) window is ideal for deep-tissue optical imaging in mammals, but lacks bright and biocompatible probes. Here, we developed biocompatible cubic-phase (alpha-phase) erbium-based rare-earth nanoparticles (ErNPs) exhibiting bright downconversion luminescence at ~1,600nm for dynamic imaging of cancer immunotherapy in mice. We used ErNPs functionalized with cross-linked hydrophilic polymer layers attached to anti-PD-L1 (programmed cell death-1 ligand-1) antibody for molecular imaging of PD-L1 in a mouse model of colon cancer and achieved tumor-to-normal tissue signal ratios of ~40. The long luminescence lifetime of ErNPs (~4.6ms) enabled simultaneous imaging of ErNPs and lead sulfide quantum dots emitting in the same ~1,600nm window. In vivo NIR-IIb molecular imaging of PD-L1 and CD8 revealed cytotoxic T lymphocytes in the tumor microenvironment in response to immunotherapy, and altered CD8 signals in tumor and spleen due to immune activation. The cross-linked functionalization layer facilitated 90% ErNP excretion within 2weeks without detectable toxicity in mice.
View details for DOI 10.1038/s41587-019-0262-4
View details for PubMedID 31570897
- Light-sheet microscopy in the near-infrared II window NATURE METHODS 2019; 16 (6): 545-+
- Molecular Imaging in the Second Near-Infrared Window ADVANCED FUNCTIONAL MATERIALS 2019; 29 (25)
Light-sheet microscopy in the near-infrared II window.
Non-invasive deep-tissue three-dimensional optical imaging of live mammals with high spatiotemporal resolution is challenging owing to light scattering. We developed near-infrared II (1,000-1,700nm) light-sheet microscopy with excitation and emission of up to approximately 1,320nm and 1,700nm, respectively, for optical sectioning at a penetration depth of approximately 750mum through live tissues without invasive surgery and at a depth of approximately 2mm in glycerol-cleared brain tissues. Near-infrared II light-sheet microscopy in normal and oblique configurations enabled in vivo imaging of live mice through intact tissue, revealing abnormal blood flow and T-cell motion in tumor microcirculation and mapping out programmed-death ligand 1 and programmed cell death protein 1 in tumors with cellular resolution. Three-dimensional imaging through the intact mouse head resolved vascular channels between the skull and brain cortex, and allowed monitoring of recruitment of macrophages and microglia to the traumatic brain injury site.
View details for PubMedID 31086342
Molecular imaging in the second near-infrared window.
Advanced functional materials
2019; 29 (25)
In the past decade, noticeable progress has been achieved regarding fluorescence imaging in the second near-infrared (NIR-II) window. Fluorescence imaging in the NIR-II window demonstrates superiorities of deep tissue penetration and high spatial and temporal resolution, which are beneficial for profiling physiological processes. Meanwhile, molecular imaging has emerged as an efficient tool to decipher biological activities on the molecular and cellular level. Extending molecular imaging into the NIR-II window would enhance the imaging performance, providing more detailed and accurate information of the biological system. In this progress report, selected achievements made in NIR-II molecular imaging are summarized. The organization of this report is based on strategies underlying rational designs of NIR-II imaging probes and their applications in molecular imaging are highlighted. This progress report may provide guidance and reference for further development of functional NIR-II probes designed for high-performance molecular imaging.
View details for DOI 10.1002/adfm.201900566
View details for PubMedID 31885529
View details for PubMedCentralID PMC6934177