Fluorescent nanocarriers targeting VCAM-1 for early detection of senescent endothelial cells

Nanomedicine. 2021 Jun:34:102379. doi: 10.1016/j.nano.2021.102379. Epub 2021 Mar 11.

Abstract

Endothelial senescence has been identified as an early event in the development of endothelial dysfunction, a hallmark of cardiovascular disease. This study developed theranostic nanocarriers (NC) decorated with VCAM-1 antibodies (NC-VCAM-1) in order to target cell surface VCAM-1, which is overexpressed in senescent endothelial cells (ECs) for diagnostic and therapeutic purposes. Incubation of Ang II-induced premature senescent ECs or replicative senescent ECs with NC-VCAM-1 loaded with lipophilic fluorescent dyes showed higher fluorescence signals than healthy EC, which was dependent on the NC size and VCAM-1 antibodies concentration, and not observed following masking of VCAM-1. NC loaded with omega 3 polyunsaturated fatty acid (NC-EPA:DHA6:1) were more effective than native EPA:DHA 6:1 to prevent Ang II-induced VCAM-1 and p53 upregulation, and SA-β-galactosidase activity in coronary artery segments. These theranostic NC might be of interest to evaluate the extent and localization of endothelial senescence and to prevent pro-senescent endothelial responses.

Keywords: Endothelial senescence and dysfunction; Nanocarriers; Omega 3 polyunsaturated fatty acid; VCAM-1.

MeSH terms

  • Animals
  • Autoantibodies / immunology
  • Cell Proliferation
  • Cellular Senescence*
  • Drug Carriers*
  • Endothelium, Vascular / cytology*
  • Endothelium, Vascular / metabolism
  • Fluorescent Dyes / chemistry*
  • Precision Medicine
  • Swine
  • Vascular Cell Adhesion Molecule-1 / immunology
  • Vascular Cell Adhesion Molecule-1 / metabolism*

Substances

  • Autoantibodies
  • Drug Carriers
  • Fluorescent Dyes
  • Vascular Cell Adhesion Molecule-1