Diatomite nanoparticles are considered a valid alternative to the synthetic porous silica ones for nano-based drug delivery systems. In article number 1800247, Luca De Stefano, Claudia Tortiglione, and co-workers explore the in vivo toxicity of hybrid diatomite nanovectors (DNPs) in a living model organism, the cnidarian freshwater polyp Hydra. The long-term effects of DNPs on Hydra, based on multiple toxicity endpoints (morphology, growth rate, apoptosis, genetic analysis), demonstrate the in vivo biosafety of this naturally derived material.