A genetic engineering strategy for editing near-infrared-II fluorophores

作者：Tian, Rui^*; Feng, Xin; Wei, Long; Dai, Daoguo; Ma, Ying; Pan, Haifeng; Ge, Shengxiang; Bai, Lang; Ke, Chaomin; Liu, Yanlin; Lang, Lixin; Zhu, Shoujun^*; Sun, Haitao; Yu, Yanbao^*; Chen, Xiaoyuan^*

来源：Nature Communications, 2022, 13(1): 2853.

DOI：10.1038/s41467-022-30304-9

• HUMAN SERUM-ALBUMIN
• SHOTGUN PROTEOMICS
• CHEMISTRY
• PLATFORM
• SPECTRA
• BRAIN
• DYE

It is currently difficult to synthesise NIR-II probes with good quantum yields, biocompatibility and pharmacokinetics. Here the authors report a strategy to alter these properties by modifying the protein coatings with biofunctional molecules, and generate long-wavelength fluorophores for in vivo imaging. @@@ The second near-infrared (NIR-II) window is a fundamental modality for deep-tissue in vivo imaging. However, it is challenging to synthesize NIR-II probes with high quantum yields (QYs), good biocompatibility, satisfactory pharmacokinetics, and tunable biological properties. Conventional long-wavelength probes, such as inorganic probes (which often contain heavy metal atoms in their scaffolds) and organic dyes (which contain large pi-conjugated groups), exhibit poor biosafety, low QYs, and/or uncontrollable pharmacokinetic properties. Herein, we present a bioengineering strategy that can replace the conventional chemical synthesis methods for generating NIR-II contrast agents. We use a genetic engineering technique to obtain a series of albumin fragments and recombinant proteins containing one or multiple domains that form covalent bonds with chloro-containing cyanine dyes. These albumin variants protect the inserted dyes and remarkably enhance their brightness. The albumin variants can also be genetically edited to develop size-tunable complexes with precisely tailored pharmacokinetics. The proteins can also be conjugated to biofunctional molecules without impacting the complexed dyes. This combination of albumin mutants and clinically-used cyanine dyes can help widen the clinical application prospects of NIR-II fluorophores.

• 单位
  吉林大学; 厦门大学