Currently, nanomaterials are of widespread use in daily commercial products. However, the most promising and potentially impacting application is in the medical field. In particular, nano-sized noble metals hold the promise to shift the current medical paradigms for the detection and therapy of neoplasms thanks to the: i) localized surface plasmon resonances (LSPRs), ii) high electron density, and iii) suitability for straightforward development of all-in-one nano-platforms. Nonetheless, there is still no clinically approved noble metal nanomaterial for cancer therapy/diagnostic. The clinical translation of noble metal nanoparticles (NPs) is mainly prevented by the issue of persistence in organism after the medical action. Such persistence increases the likelihood of toxicity and the interference with common medical diagnoses. Size-reduction to ultrasmall nanoparticles (USNPs) is a suitable approach to promote metal excretion by the renal pathway. However, most of the functionalities of NPs are lost or severely altered in USNPs, jeopardizing clinical applications. A groundbreaking advance to jointly combine the appealing behaviors of NPs with metal excretion relies on the ultrasmall-in-nano approach for the design of all-in-one degradable nano-platforms comprising USNPs. Such nano-architectures might lead to the delivery of a novel paradigm for nanotechnology, enabling the translation of noble metal nanomaterials to clinics in order to treat carcinomas in a less invasive and more efficient manner. This review covers the recent progresses related to this exciting approach. The most significant nano-architectures designed with the ultrasmall-in-nano approach are discussed, and their applicative perspectives provided.

Passion fruit-like nano-architectures (NAs) are all-in-one platforms of increasing interest for the translation of metal nanoparticles into clinics. NAs are nature-inspired disassembling inorganic theranostics, which jointly combine most of the appealing behaviors of noble metal nanoparticles with their potential organism excretion. Despite their unique and promising properties, NAs in vivo interactions and potential adverse effects have not yet been investigated. In this study, we employ zebrafish (Danio Rerio) to assess the development toxicity of NAs as well as their uptake and bioaccumulation at different stages of growth. The evaluation of multiple endpoints related to the toxicity clearly indicates that NAs do not induce mortality, developmental defects, or alterations on the hatching rate and behavior of zebrafish. Moreover, the analysis of nanostructures uptake and biodistribution demonstrates that NAs are successfully internalized and present a specific localization. Overall, our results demonstrate that NAs are able to pass through the embryos chorion and accumulate in specific tissues, exhibiting an impressive biocompatibility.