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.
Highlights
Carbon monoxide releasing molecules (CORMs) are drugs that are examined to explicitly convey carbon monoxide (CO) to unhealthy or aggravated tissues to start and advance remedial impacts at the site of disease
Our study indicates that CORMs chemisorbed on diatom frustules retain their CO-releasing abilities and that they are rapidly released from the same
We show that 3D FT-IR spectroscopic imaging is a powerful technique to help to elucidate CORM localization and reactivity on silica-based materials and that both CO-releasing molecules show a concentration-dependent effect on the neovascularization in developing zebrafish
Summary
Carbon monoxide releasing molecules (CORMs) are drugs that are examined to explicitly convey carbon monoxide (CO) to unhealthy or aggravated tissues to start and advance remedial impacts at the site of disease. The molecules are known to reverse the inhibition of mitochondrial biogenesis [11,12,13,14,15] and prevent doxorubicin-induced cardiac cell death [16,17]. CORM-2 and CORM-3, e.g., exert in vivo a positive effect in doxorubicin (Dox)-induced cardiomyopathy. CORM-2 protects the myocardium from Dox exposure by decreasing apoptosis and oxidative stress, while CORM-3, in a rat model of Dox-induced cardiomyopathy, induces a positive inotropic effect by increasing systolic pressure of the heart [17].
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