体内
癌症免疫疗法
免疫疗法
临床前影像学
肿瘤微环境
分子成像
CD8型
材料科学
癌症研究
生物物理学
免疫系统
化学
医学
生物
免疫学
生物技术
作者
Yeteng Zhong,Zhuoran Ma,Feifei Wang,Wang Xi,Yijun Yang,Yulai Liu,Xiang Zhao,Jiachen Li,Haotian Du,Mingxi Zhang,Qiuhong Cui,Shoujun Zhu,Qinchao Sun,Hao Wan,Ye Tian,Qiang Liu,Weizhi Wang,K. Christopher García,Hongjie Dai
标识
DOI:10.1038/s41587-019-0262-4
摘要
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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