Effective excretion of nanostructured noble metals is still one of the most challenging bottlenecks for their employment in clinical practice. Besides the persistence issue, the clinical translation of inorganic nanomaterials is also affected by a bewildering lack of investigations regarding their quantitative biokinetics. Here, we have quantitatively correlated the chemical nature of the three most interesting noble metals for biomedical applications to their biosafety and biokinetics in, respectively, zebrafish and murine models. Gold, silver, and platinum ultrasmall-in-nano architectures with comparable size elicit, after intravenous administration, different excretion pathways depending on their intrinsic metallic nature. Understanding the in vivo fate of noble metal nanoparticles is a significant breakthrough to unlock their clinical employment for the establishment of treatments for neoplasms, infectious diseases, and neurological disorders.

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Nanomaterials have attracted increasing interest for their potentiality to revolutionize the diagnosis and treatment of many diseases, especially neoplasms. Interestingly, there is a huge imbalance between the number of proposed nanoplatforms and the few ones approved for clinical applications. This disequilibrium affects in particular noble metal nanoparticles (NPs), that present no-approved platform and very few candidates in clinical trials because of the issue of persistence. In this perspective, we discuss if nanomedicine is generally keeping its promises with a focus on the approach that could fill the gap between NPs and oncology in the next future: the ultrasmall-in-nano.