Tissue Clearing and Its Application in Nanoparticle Development

Abstract Nanoparticles are widely used in biomedical applications due to their small size, large surface area, and unique physicochemical properties. These characteristics make them ideal for drug delivery, diagnostic imaging, and therapeutic interventions. Their ability to interact with biological systems at the cellular and molecular levels enables targeted treatments. Understanding the biodistribution of nanoparticles at the cellular level within whole organisms is crucial for assessing their safety and effectiveness; however, proper technologies have been lacking to achieve this. For example, traditional imaging techniques like magnetic resonance imaging (MRI) and computed tomography (CT) often lack the resolution needed, while tissue‐section‐based methods miss the whole‐body systemic view. Recent tissue clearing methods have emerged as a promising solution for 3D visualization of nanoparticles in entire organs, as they enable cellular‐level imaging of whole organisms without the need for sectioning. This review explores advancements in diverse tissue clearing techniques and their application in studying nanoparticle biodistribution, providing insights crucial for the development of nanoparticle‐based therapies.