美国斯坦福大学Hongjie Dai团队的一项最新研究使用超亮近红外IIb（NIR-IIb）稀土纳米颗粒对免疫疗法进行体内分子成像。相关论文2019年9月30日在线发表在《自然—生物技术》。

研究人员开发了生物相容性的立方相（α相）-基稀土纳米粒子（ErNPs），在大约1600 nm处显示出明亮的下转换发光，用于小鼠癌症免疫疗法的动态成像。研究人员使用带有抗PD-L1（程序性细胞死亡1配体-1）抗体的交联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，并实现了肿瘤至正常组织信号比约为40。ErNPs的长发光寿命（约4.6µms）可实现在同一1600nm窗口内发射的ErNPs和硫化铅量子点的同时成像。

PD-L1和CD8的体内NIR-IIb分子成像显示，在肿瘤微环境中对免疫疗法的响应的细胞毒性T淋巴细胞，并且由于免疫激活而改变了肿瘤和脾脏中的CD8信号。交联的功能化层可在2周内促进90％的ErNP排出体外，并且在小鼠中没有可检测到的毒性。

据介绍，NIR-IIb（1,500–1,700nm）窗口是哺乳动物深层组织光学成像的理想选择，但缺少明亮且生物相容的探针。

附：英文原文

Title: In vivo molecular imaging for immunotherapy using ultra-bright near-infrared-IIb rare-earth nanoparticles

Author: Yeteng Zhong, Zhuoran Ma, Feifei Wang, Xi Wang, 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 Garcia, Hongjie Dai

Issue&Volume: 2019-09-30

Abstract: The near-infrared-IIb (NIR-IIb) (1,5001,700nm) window is ideal for deep-tissue optical imaging in mammals, but lacks bright and biocompatible probes. Here, we developed biocompatible cubic-phase (-phase) erbium-based rare-earth nanoparticles (ErNPs) exhibiting bright downconversion luminescence at ~1,600nm 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 (~4.6ms) enabled simultaneous imaging of ErNPs and lead sulfide quantum dots emitting in the same ~1,600nm 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 2weeks without detectable toxicity in mice. 

DOI: 10.1038/s41587-019-0262-4

Source: https://www.nature.com/articles/s41587-019-0262-4