Thrombin-activatable fluorescent peptide incorporated gold nanoparticles for dual optical/computed tomography thrombus imaging

Sung Pil Kwon, Sangmin Jeon, Sung Hoon Lee, Hong Yeol Yoon, Ju Hee Ryu, Dayil Choi, Jeong Yeon Kim, Jiwon Kim, Jae Hyung Park, Dong Eog Kim, Ick Chan Kwon, Kwang Meyung Kim, Cheol Hee Ahn

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Abstract

Thrombosis is an important pathophysiologic phenomenon in various cardiovascular diseases, which can lead to oxygen deprivation and infarction of tissues by generation of a thrombus. Thus, direct thrombus imaging can provide beneficial in diagnosis and therapy of thrombosis. Herein, we developed thrombin-activatable fluorescent peptide (TAP) incorporated silica-coated gold nanoparticles (TAP-SiO2@AuNPs) for direct imaging of thrombus by dual near-infrared fluorescence (NIRF) and micro-computed tomography (micro-CT) imaging, wherein TAP molecules were used as targeted thrombin-activatable peptide probes for thrombin-specific NIRF imaging. The freshly prepared TAP-SiO2@AuNPs had an average diameter of 39.8 ± 2.55 nm and they showed the quenched NIRF signal in aqueous condition, due to the excellent quenching effect of TAP molecules on the silica-gold nanoparticle surface. However, 30.31-fold higher NIRF intensity was rapidly recovered in the presence of thrombin in vitro, due to the thrombin-specific cleavage of quenched TAP molecules on the gold particle surface. Furthermore, TAP-SiO2@AuNPs were successfully accumulated in thrombus by their particle size-dependent capturing property, and they presented a potential X-ray absorption property in a dose-dependent manner. Finally, thrombotic lesion was clearly distinguished from peripheral tissues by dual NIRF/micro-CT imaging after intravenous injection of TAP-SiO2@AuNPs in the in situ thrombotic mouse model, simultaneously. This study showed that thrombin-activatable fluorescent peptide incorporated silica-coated gold nanoparticles can be potentially used as a dual imaging probe for direct thrombus imaging and therapy in clinical applications.

Original languageEnglish
Pages (from-to)125-136
Number of pages12
JournalBiomaterials
Volume150
DOIs
Publication statusPublished - 2018 Jan 1

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Keywords

  • Dual optical/CT imaging
  • Silica-coated gold nanoparticle
  • Thrombin-activatable fluorescent probe
  • Thrombus imaging

ASJC Scopus subject areas

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Cite this

Kwon, S. P., Jeon, S., Lee, S. H., Yoon, H. Y., Ryu, J. H., Choi, D., Kim, J. Y., Kim, J., Park, J. H., Kim, D. E., Kwon, I. C., Kim, K. M., & Ahn, C. H. (2018). Thrombin-activatable fluorescent peptide incorporated gold nanoparticles for dual optical/computed tomography thrombus imaging. Biomaterials, 150, 125-136. https://doi.org/10.1016/j.biomaterials.2017.10.017