## 4 Conclusions  
In conclusion, we showed via FT-IR spectromicroscopy imaging that Re-based CORMs can be chemisorbed on diatom frustules without affecting their CO-releasing properties and that the same rapidly discharged the molecules in PBS buffer. Both CORMS showed a concentration-dependent effect on the neovascularization in developing zebrafish. Angiogenesis stimulation was observed at lower drug doses (<25 m) while angiogenesis inhibition at the higher doses. B\({}_{12}\)-ReFORM-2 revealed more profound effects than ReFORM-2. Neither the CORMs, nor the diatom carriers, showed any sign of toxicity in vivo at very high doses. In particular, the materials stimulated no inflammatory reaction as the major tissue response to the exogenous administration. Both of these properties could be beneficial for their potential therapeutic application, e.g., the stimulation of wound healing (expected to occur upon lower doses) or the anticancer effect (expected at higher doses). In the future, we plan to evaluate the effects of the molecules and loaded diatoms on doxorubicin-induced cardiac cell death.  
The following are available online at [[http://www.mdpi.com/2076-3417/10/20/7380/s1](http://www.mdpi.com/2076-3417/10/20/7380/s1)]([http://www.mdpi.com/2076-3417/10/20/7380/s1](http://www.mdpi.com/2076-3417/10/20/7380/s1)), Figure S1: The suppression of neovascularization in developing zebrafish embryos by ReFORM-2 and B\({}_{12}\)-ReFORM-2 treatments assessed according to the ISV vessels development at 48 hpf. Suppressed ISVs angiogenesis was indicated by red dashed arrows, while white arrow indicates the vessels in the hematopoietic tissue that increased fluorescence compared to the control ones seemed to be stimulated, Table S1: Lethal and teratogenic effects observed in zebrafish (_Danio rerio_) embryos at different hours post-fertilization (hpf).  
Conceptualization, A.P. and F.Z.; methodology, J.D. and N.R.; software, all authors; validation, A.P. and F.Z.; formal analysis, all authors; investigation, all authors; resources, A.P. and F.Z.; data curation, J.D. and N.R.; writing--original draft preparation, J.D. and N.R.; writing--review and editing, A.P. and F.Z.; supervision, A.P. and F.Z.; project administration, A.P. and F.Z.; funding acquisition, A.P. and F.Z. All authors have read and agreed to the published version of the manuscript.  
Financial support from the Swiss National Science Foundation (Grant# PP00P2_170589 to J.D. and F.Z.), the Canton of Fribourg (1259-0001 to J.D.), and the Institute of Molecular Genetics and Genetic Engineering from the University of Belgrade (Ministry of Education, Science and Technological Development of the Republic of Serbia, Project No.173048 (to N.R. and A.P.) are gratefully acknowledged.  
The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.  
Figure 8: Inflammatory response in \(T_{\text{g}}(mpx\text{:EGFP})\) embryos after the 114-h exposure to the silicate diatoms (13 and 20 m in size). Fluorescence intensity of EGFP-labelled neutrophils (**A**) and morphology and neutrophils occurrence within the body of the exposed embryos (**B**) are shown.