美國斯坦福大學(xué)Hongjie Dai團(tuán)隊的一項(xiàng)最新研究使用超亮近紅外IIb（NIR-IIb）稀土納米顆粒對免疫療法進(jìn)行體內(nèi)分子成像。相關(guān)論文2019年9月30日在線發(fā)表在《自然—生物技術(shù)》。

研究人員開發(fā)了生物相容性的立方相（α相）-基稀土納米粒子（ErNPs），在大約1600 nm處顯示出明亮的下轉(zhuǎn)換發(fā)光，用于小鼠癌癥免疫療法的動態(tài)成像。研究人員使用帶有抗PD-L1（程序性細(xì)胞死亡1配體-1）抗體的交聯(lián)親水聚合物層功能化的ErNPs在結(jié)腸癌小鼠模型中對PD-L1進(jìn)行分子成像，并實(shí)現(xiàn)了腫瘤至正常組織信號比約為40。ErNPs的長發(fā)光壽命（約4.6?ms）可實(shí)現(xiàn)在同一1600nm窗口內(nèi)發(fā)射的ErNPs和硫化鉛量子點(diǎn)的同時成像。

PD-L1和CD8的體內(nèi)NIR-IIb分子成像顯示，在腫瘤微環(huán)境中對免疫療法的響應(yīng)的細(xì)胞毒性T淋巴細(xì)胞，并且由于免疫激活而改變了腫瘤和脾臟中的CD8信號。交聯(lián)的功能化層可在2周內(nèi)促進(jìn)90％的ErNP排出體外，并且在小鼠中沒有可檢測到的毒性。

據(jù)介紹，NIR-IIb（1,500–1,700nm）窗口是哺乳動物深層組織光學(xué)成像的理想選擇，但缺少明亮且生物相容的探針。

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