期刊
ADVANCED FUNCTIONAL MATERIALS
卷 28, 期 50, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.201804956
关键词
molecular imaging; NIR-II fluorophore; PD-L1; renal excretion
类别
资金
- National Science Foundation of China [21772084, 21603074, 11774094]
- Chenguang Program by Shanghai Education Development Foundation
- Shanghai Municipal Education Commission [16CG25]
- National Institutes of Health [DP1-NS-105737]
- Calbrain program
- Shenzhen Peacock Program Grant [KQTD20140630160825828]
Fluorescence imaging in the second near-infrared (NIR-II) window holds impressive advantages of enhanced penetration depth and improved signal-to-noise ratio. Bright NIR-II fluorophores with renal excretion ability and low tissue accumulation are favorable for in vivo molecular imaging applications as they can render the target-mediated molecular imaging process easily distinguishable. Here, a probe (anti-PD-L1-BGP6) comprising a fluorophore (IR-BGP6) covalently bonded to the programmed cell death ligand-1 monoclonal antibody (PD-L1 mAb) for molecular imaging of immune checkpoint PD-L1 (a targeting site upregulated in various tumors for cancer imaging) in the NIR-II window is reported. Through molecular optimization, the bright NIR-II fluorophore IR-BGP6 with fast renal excretion (approximate to 91% excretion in general through urine within the first 10 h postinjection) is developed. The conjugate anti-PD-L1-BGP6 succeeds in profiling PD-L1 expression and realizes efficient noninvasive molecular imaging in vivo, achieving a tumor to normal tissue (TINT) signal ratio as high as approximate to 9.5. Compared with the NIR-II fluorophore with high nonspecific tissue accumulation, IR-BGP6 derived PD-L1 imaging significantly enhances the molecular imaging performance, serving as a strong tool for potentially studying underlying mechanism of immunotherapy. The work providesrationales to design renal-excreted NIR-II fluorophores and illustrate their advantages for in vivo molecular imaging.
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