Neovascularization Effects of Carbon Monoxide Releasing Drugs Chemisorbed on Coscinodiscus Diatoms Carriers Characterized by Spectromicroscopy Imaging

Abstract

Silica microparticles made of diatomaceous earth have become particularly attractive materials for designing drug delivery systems. In order to investigate the use of natural diatoms as drug scaffolds for carbon monoxide releasing molecules (CORMs), we evaluated the chemisorption of the cis-[Re(CO)2Br4]2− complex (ReCORM-2) and its vitamin B12 derivative (B12-ReCORM-2) on Coscinodiscus frustules by 3D FT-IR spectroscopic imaging, and the drugs’ neovascularization effects in vivo in the zebrafish (Danio rerio) model. By mapping the symmetric Re-C≡O υ(CO) stretching vibration of the CORMs in the 2000 cm−1 region, we found that the drugs are mostly localized at the girdle band of the diatom frustule. Both ReCORM-2 and B12-ReCORM-2 retain their CO-releasing ability when chemisorbed on the diatoms. When applied in vivo at doses ≥25 µM, the molecules markedly reduced intersegmental and subintestinal vessels development in zebrafish, revealing high anti-angiogenic potential. In addition, diatom frustules did not provoke any toxic in vivo response in the zebrafish embryos, including inflammation. Overall, our results indicate that: (1) CORMs chemisorbed on diatom frustules retain their CO-releasing abilities; (2) both CO-releasing molecules show a concentration-dependent effect on the neovascularization in developing zebrafish; (3) silicate frustules are not toxic and could be used as CORMs drug carriers.