期刊
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 142, 期 15, 页码 7075-7082出版社
AMER CHEMICAL SOC
DOI: 10.1021/jacs.0c00659
关键词
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资金
- Nanyang Technological University [NTU-SUG: M4081627]
- Singapore Ministry of Education Academic Research Fund [2017-T1-002-134, RG147/17, 2019-T1-002-045, RG125/19, MOE2018-T2-2-042]
Real-time imaging of immunoactivation is imperative for cancer immunotherapy and drug discovery; however, most existing imaging agents possess always-on signals and thus have poor signal correlation with immune responses. Herein, renalclearable near-infrared (NIR) fluorescent macromolecular reporters are synthesized to specifically detect an immunoactivation-related biomarker (granzyme B) for real-time evaluation of cancer immunotherapy. Composed of a peptide-caged NIR signaling moiety linked with a hydrophilic poly(ethylene glycol) (PEG) passivation chain, the reporters not only specifically activate their fluorescence by granzyme B but also passively target the tumor of living mice after systemic administration. Such granzyme B induced in vivo signals of the reporters are validated to correlate well with the populations of cytotoxic T lymphocytes (CD8(+)) and T helper (CD4(+)) cells detected in tumor tissues. By virtue of their ideal renal clearance efficiency (60% injected doses at 24 h postinjection), the reporters can be used for optical urinalysis of immunoactivation simply by detecting the status of excreted reporters. This study thus proposes a molecular optical imaging approach for noninvasive evaluation of cancer immunotherapeutic efficacy in living animals.
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