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In vivo molecular imaging for immunotherapy using ultra-bright near-infrared-IIb rare-earth nanoparticles
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In vivo molecular imaging for immunotherapy using ultra-bright near-infrared-IIb rare-earth nanoparticles
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Journal Article
In vivo molecular imaging for immunotherapy using ultra-bright near-infrared-IIb rare-earth nanoparticles
2019
Overview
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.
Biocompatible rare-earth nanoparticles with an emission maximum at 1,600 nm enable sensitive in vivo imaging.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Animals
/ Antineoplastic Agents, Immunological - administration & dosage
/ Antineoplastic Agents, Immunological - chemistry
/ Antineoplastic Agents, Immunological - pharmacology
/ Biomedical and Life Sciences
/ Biomedical Engineering/Biotechnology
/ Cancer
/ Colon
/ Colonic Neoplasms - drug therapy
/ Colonic Neoplasms - immunology
/ Erbium
/ Imaging
/ Methods
/ Mice
/ Molecular diagnostic techniques
/ Polymers
/ Spleen
/ Sulfides
/ T-Lymphocytes, Cytotoxic - immunology
/ Toxicity
/ Tumor Microenvironment - drug effects
/ Tumors
