Photoactivatable Aptamer-CRISPR Nanodevice Enables Precise Profiling of Interferon-Gamma Release in Humanized Mice

#Phorbol 12-myristate 13-acetate (PMA) ; #Ionomycin Calcium Salt ; #Brefeldin A ;  #1652981 ; #5608212 ; #2031560 ;  

ACS Nano. 2024 Jan 30;18(4):3826-3838.

Zheng Liu 1Xiang Duan 2Yangfang Yun 1Siqi Li 2Zhiyuan Feng 1Jiayin Zhan 1Ran Liu 1Yan Li 2Jingjing Zhang 1

Affiliations expand

Abstract

Real-time dynamic imaging of immunoactivation-related cytokines is crucial for evaluating the efficacy of immune checkpoint blockade therapy and optimizing the treatment regimen. We introduce herein a spatiotemporally controlled nanodevice that allows in situ photoactivated imaging of interferon-gamma (IFN-γ) secretion from T cells in vitro and in vivo. The nanodevice is constructed by rational engineering of an aptamer-embedded, UV-cleavable PC-DNA probe and further integration with upconversion nanoparticles- and CRISPR-Cas12a-enhanced fluorescence systems. Using human peripheral blood mononuclear cells (PBMC)-engrafted mouse models, this nanodevice allows for the quantitative imaging of endogenous IFN-γ and its intratumoral dynamics responding to antiprogrammed cell death receptor 1 (anti-PD-1) therapy. This study thus provides a toolbox for boosting the sensitivity and precision of cytokine imaging during immune checkpoint blockade therapy, enlightening research toward imaging-guided tumor therapy.

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