A Fibrin Site-Specific Nanoprobe for Imaging Fibrin-Rich Thrombi and Preventing Thrombus Formation in Venous Vessels

Adv Mater. 2022 Apr;34(16):e2109955. doi: 10.1002/adma.202109955. Epub 2022 Mar 14.

Abstract

Venous thromboembolism (VTE) is a prevalent public health issue worldwide. Before treatment, spatiotemporally accurate thrombus detection is essential. However, with the currently available imaging technologies, this is challenging. Herein, the development of a novel fibrin-specific nanoprobe (NP) based on the conjugation of poly(lactic-co-glycolic acid) with the pentapeptide Cys-Arg-Glu-Lys-Ala (CREKA) for selective and semiquantitative imaging in vivo is presented. By integrating Fe3 O4 and NIR fluorochrome (IR780), the NP can function as a highly sensitive sensor for the direct analysis of thrombi in vivo. The fibrin-specific NP distinguishes fibrin-rich thrombi from collagen-rich or erythrocyte-rich thrombi, which can be beneficial for future individually tailored therapeutic strategy. Furthermore, loading NPs with the ketotifen fumarate results in mast cell degranulation inhibition, and hence, NPs can prevent thrombosis without the risk of excessive bleeding. Thus, the use of fibrin-specific NPs may serve as a safe alternative approach for the detection and prevention of VTEs in susceptible populations in the future.

Keywords: fibrin; image-guided therapy; multimodal imaging; targeted nanoprobes; thrombus prevention.

MeSH terms

  • Diagnostic Imaging
  • Erythrocytes
  • Fibrin*
  • Humans
  • Thrombosis* / diagnostic imaging
  • Thrombosis* / prevention & control

Substances

  • Fibrin