Microbubble‐encapsulated Cobalt Nitrato Complexes for Ultrasound‐triggerable Nitric Oxide Delivery

ChemMedChem, vol. 19, pp. e202400232

Abstract

Abstract Cobalt complexes exhibit versatile reactivity with nitric oxide (NO), enabling their utilization in applications ranging from homogeneous catalysis to NO‐based modulation of biological processes. However, the coordination geometry around the cobalt center is complex, the therapeutic window of NO is narrow, and controlled NO delivery is difficult. To better understand the complexation of cobalt with NO, we prepared four cobalt nitrato complexes and present a structure‐property relationship for ultrasound‐triggerable NO release. We hypothesized that modulation of the coordination geometry by ligand‐modification would improve responsiveness to mechanical stimuli, like ultrasound. To enable eventual therapeutic testing, we here first demonstrate the in vitro tolerability of [Co(ethylenediamine) 2 (NO)(NO 3 )](NO 3 ) in A431 epidermoid carcinoma cells and J774A.1 murine macrophages, and we subsequently show successful encapsulation of the complex in poly(butyl cyanoacrylate) microbubbles. These hybrid Co‐NO‐containing microbubbles may in the future aid in ultrasound imaging‐guided treatment of NO‐responsive vascular pathologies.

Authors 7

1. Patrick Koczera Aachen Institute for Experimental Molecular Imaging Medical Faculty

   RWTH Aachen University

   Affiliation as printed

   Institute for Experimental Molecular Imaging Medical Faculty RWTH Aachen University Aachen Germany

   Institute for Experimental Molecular Imaging Medical Faculty RWTH Aachen University Aachen Germany

2. Fabian Thomas Aachen Institute of Inorganic Chemistry

   RWTH Aachen University

   Affiliation as printed

   Institute of Inorganic Chemistry RWTH Aachen University Aachen Germany

   Institute of Inorganic Chemistry RWTH Aachen University Aachen Germany

3. Elena Rama Aachen Institute for Experimental Molecular Imaging Medical Faculty

   RWTH Aachen University

   Affiliation as printed

   Institute for Experimental Molecular Imaging Medical Faculty RWTH Aachen University Aachen Germany

   Institute for Experimental Molecular Imaging Medical Faculty RWTH Aachen University Aachen Germany

4. Sven Thoröe‐Boveleth Aachen Institute for Occupational, Social, and Environmental Medicine Medical Faculty

   RWTH Aachen University

   Affiliation as printed

   Institute for Occupational Social and Environmental Medicine Medical Faculty RWTH Aachen University Aachen Germany

   Institute for Occupational Social and Environmental Medicine Medical Faculty RWTH Aachen University Aachen Germany

5. Fabian M. Kiessling Aachen Institute for Experimental Molecular Imaging Medical Faculty

   RWTH Aachen University

   Affiliation as printed

   Institute for Experimental Molecular Imaging Medical Faculty RWTH Aachen University Aachen Germany

   Institute for Experimental Molecular Imaging Medical Faculty RWTH Aachen University Aachen Germany

6. Twan Lammers corresponding Aachen Institute for Experimental Molecular Imaging Medical Faculty

   RWTH Aachen University

   Affiliation as printed

   Institute for Experimental Molecular Imaging Medical Faculty RWTH Aachen University Aachen Germany

   RWTH Aachen University Medical Faculty: Rheinisch-Westfalische Technische Hochschule Aachen Medizinische Fakultat, Experimental Molecular Imaging, Forckenbeckstrasse 55, 52074 Aachen, GERMANY

7. Sonja Herres‐Pawlis Aachen Institute of Inorganic Chemistry

   RWTH Aachen University

   Affiliation as printed

   Institute of Inorganic Chemistry RWTH Aachen University Aachen Germany

   Institute of Inorganic Chemistry RWTH Aachen University Aachen Germany