In vivo molecular imaging for immunotherapy using ultra-bright near-infrared-IIb rare-earth nanoparticles
Open accessAbstract
The near-infrared-IIb (NIR-IIb) (1,500-1,700 nm) window is ideal for deep-tissue optical imaging in mammals, but lacks bright and biocompatible probes. Here, we developed biocompatible cubic-phase (α-phase) erbium-based rare-earth nanoparticles (ErNPs) exhibiting bright downconversion luminescence at ~1,600 nm 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 (~4.6 ms) enabled simultaneous imaging of ErNPs and lead sulfide quantum dots emitting in the same ~1,600 nm 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 2 weeks without detectable toxicity in mice.
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- Authors
- Zhong, Y., Ma, Z., Wang, F., Wang, X., Yang, Y., Liu, Y., Zhao, X., Li, J., Du, H., Zhang, M., Cui, Q., Zhu, S., Sun, Q., Wan, H., Tian, Y., Liu, Q., Wang, W., Garcia, K. C., & Dai, H.
- Affiliations
- Stanford University (US)
- Beijing Jiaotong University (CN)
- Stanford Medicine (US)
- Corresponding author
- Dai, Hongjie
- ORCID
- Venue
- Nature Biotechnology
- Published
- 2019-09-30
- Volume
- 37
- Issue
- 11
- Pages
- 1322-1331
- ISSN
- 0733-222X (ISSN-L)
- 1087-0156
- 1546-1696
- PMC
- PMC6858548
- OpenAlex
- W2975715205
- Cited by
- 575
- References
- 59
- Citations by year
- 2026: 32 · 2025: 83 · 2024: 78 · 2023: 109 · 2022: 107 · 2021: 101 · 2020: 60 · 2019: 4
- FWCI
- 24.54
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Biotechnology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Health & Human Services | National Institutes of Health (DP1-NS-105737)
- Topics
- Physical Sciences › Materials Science › Materials Chemistry › Luminescence Properties of Advanced Materials
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Optical Imaging and Spectroscopy Techniques
- Keywords
- rare earth nanoparticles, down-conversion luminescence, cancer immunotherapy, PD-L1 imaging, PD-L1 inhibitors, colon cancer, cytotoxic T lymphocytes, CD8, tumor microenvironment, PbS quantum dots, nanoparticle biocompatibility, nanoparticle clearance
- MeSH terms
- Antineoplastic Agents, Immunological, Animals, Colonic Neoplasms, Erbium, Immunotherapy, Infrared Rays, T-Lymphocytes, Cytotoxic, CD8 Antigens, Xenograft Model Antitumor Assays, Quantum Dots, Cell Line, Tumor, Mice, Nanoparticles, Tumor Microenvironment, B7-H1 Antigen, Optical Imaging
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Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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