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Published on: June 14, 2018
Photoactivatable Aptamer-CRISPR Nanodevice Enables Precise Profiling of Interferon-Gamma Release in Humanized Mice
Zheng Liu1, Xiang Duan2, Yangfang Yun1
1State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University, Nanjing 210023, China.
Insights
This study presents a novel nanodevice for real-time imaging of interferon-gamma (IFN-γ) secretion from T cells. This tool enhances the evaluation of immune checkpoint blockade therapy efficacy in cancer treatment.
Area of Science:
- Biomedical Engineering
- Immunology
- Nanotechnology
Background:
- Real-time cytokine imaging is vital for assessing immune checkpoint blockade therapy effectiveness.
- Optimizing cancer treatment regimens requires precise monitoring of immune responses.
Purpose of the Study:
- To develop a nanodevice for spatiotemporally controlled, *in situ* photoactivated imaging of interferon-gamma (IFN-γ) secretion.
- To enable quantitative imaging of endogenous IFN-γ dynamics in response to anti-PD-1 therapy.
Main Methods:
- Engineered an aptamer-embedded, UV-cleavable PC-DNA probe integrated with upconversion nanoparticles and CRISPR-Cas12a.
- Utilized human peripheral blood mononuclear cells (PBMC)-engrafted mouse models for *in vitro* and *in vivo* studies.
- Performed quantitative imaging of endogenous IFN-γ and its intratumoral dynamics.
Main Results:
- Successfully demonstrated *in situ* photoactivated imaging of IFN-γ secretion from T cells.
- Quantitatively imaged endogenous IFN-γ dynamics in response to anti-PD-1 therapy in mouse models.
- Validated the nanodevice's capability for sensitive and precise cytokine imaging.
Conclusions:
- The developed nanodevice offers a powerful tool for enhancing sensitivity and precision in cytokine imaging during immune checkpoint blockade therapy.
- This technology provides insights into imaging-guided tumor therapy and optimizing treatment strategies.
- The study highlights a novel approach for monitoring T cell-mediated immune responses in cancer therapy.
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.
