In vivo molecular imaging for immunotherapy using ultra-bright near-infrared-IIb rare-earth nanoparticles
In vivo molecular imaging for immunotherapy using ultra-bright near-infrared-IIb rare-earth nanoparticles
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DOI：
10.1038/s41587-019-0262-4
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发表时间：
2019-11-01
影响因子：
46.9
通讯作者：
Dai, Hongjie
中科院分区：
文献类型：
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作者：
Zhong, Yeteng;Ma, Zhuoran;Dai, Hongjie
近红外-IIb(NIR-IIb)(1,500-1,700 nm)窗口是哺乳动物深层组织光学成像的理想窗口，但缺乏明亮和生物兼容的探针。在这里，我们开发了生物相容的立方相(a相)铒稀土纳米颗粒(ErNPs)，它在类似于1,600 nm处显示出明亮的下转换发光，用于小鼠癌症免疫治疗的动态成像。我们使用连接到抗PD-L1(程序性细胞死亡-1配体-1)抗体上的交联型亲水聚合物层功能化的ErNPs在结肠癌小鼠模型中对PD-L1进行分子成像，获得了接近40的肿瘤与正常组织信号比。ErNPs的长发光寿命(类似于4.6ms)使其能够同时成像在相同的类似于1600 nm窗口中发射的ErNPs和硫化铅量子点。在体内，PD-L1和CD8的NIR-IIb分子成像显示免疫治疗后肿瘤微环境中的细胞毒性T细胞，并由于免疫激活而改变了肿瘤和脾中的CD8信号。该交联官能化层在2周内促进了90%的ErNP的排泄，在小鼠体内没有检测到毒性。
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 (a-phase) erbium-based rare-earth nanoparticles (ErNPs) exhibiting bright downconversion luminescence at similar to 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 similar to 40. The long luminescence lifetime of ErNPs (similar to 4.6 ms) enabled simultaneous imaging of ErNPs and lead sulfide quantum dots emitting in the same similar to 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.