In Vivo Fate of Diatom-Based Nanocarriers: Advances, Challenges, and Future Perspectives.

Diatom nanotechnology offers significant potential for the development of innovative diatom-based nanocarriers for drug delivery and bioimaging, with promising implications for the treatment and diagnosis of diverse diseases. However, clinical translation of these nanocarriers remains limited due to an incomplete understanding of their in vivo fate. Current studies on the biodistribution, intracellular behavior, biodegradation, and clearance of diatom-based nanocarriers are inadequate and often lack systematic evaluation, leaving critical knowledge gaps. A comprehensive understanding of how these nanocarriers traverse biological barriers, interact with cellular components, and are ultimately eliminated from the body is essential for their rational design and safe clinical implementation. This perspective critically examines the in vivo fate of diatom-based nanocarriers, highlighting recent advances while identifying key challenges and unresolved questions. By integrating insights into their biodistribution, intracellular interactions, toxicological profile, biodegradation, and clearance mechanisms, this article provides a framework to guide the development of more effective and clinically relevant diatom-based nanoplatforms. Furthermore, it outlines future research directions and design strategies for next-generation nanoformulations, aiming to accelerate their translation from bench to the bedside.