Nature biotechnology, 2019-11, Vol.37 (11), p.1322-1331
2019
Details
- Autor(en) / Beteiligte
- Titel
- In vivo molecular imaging for immunotherapy using ultra-bright near-infrared-IIb rare-earth nanoparticles
- Ist Teil von
- Nature biotechnology, 2019-11, Vol.37 (11), p.1322-1331
- Ort / Verlag
- United States: Nature Publishing Group
- Erscheinungsjahr
- 2019
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1087-0156eISSN: 1546-1696DOI: 10.1038/s41587-019-0262-4Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6858548
- Format
- –
- Schlagworte
- Animals, Antibodies, Antineoplastic Agents, Immunological - administration & dosage, Antineoplastic Agents, Immunological - chemistry, Antineoplastic Agents, Immunological - pharmacology, Apoptosis, B7-H1 Antigen - immunology, Biocompatibility, Biomedical materials, Cancer, Cancer immunotherapy, CD8 antigen, CD8 Antigens - metabolism, Cell death, Cell Line, Tumor, Colon, Colon cancer, Colonic Neoplasms - drug therapy, Colonic Neoplasms - immunology, Crosslinking, Cytotoxicity, Erbium, Erbium - chemistry, I.R. radiation, Imaging, Immune response, Immunotherapy, Infrared Rays, Lead sulfides, Luminescence, Lymphocytes, Lymphocytes T, Methods, Mice, Molecular diagnostic techniques, Nanoparticles, Optical Imaging, PD-1 protein, PD-L1 protein, Quantum Dots, Rare earth elements, Rare earth metals, Spleen, Sulfide, T-Lymphocytes, Cytotoxic - immunology, Toxicity, Tumor Microenvironment - drug effects, Tumors, Xenograft Model Antitumor Assays