Tailoring Renal Clearance and Tumor Targeting of Ultrasmall Metal Nanoparticles with Particle Density

Abstract Identifying key factors that govern the in vivo behavior of nanomaterials is critical to the clinical translation of nanomedicines. Overshadowed by size‐, shape‐, and surface‐chemistry effects, the impact of the particle core density on clearance and tumor targeting of inorganic nanoparticles (NPs) remains largely unknown. By utilizing a class of ultrasmall metal NPs with the same size and surface chemistry but different densities, we found that the renal‐clearance efficiency exponentially increased in the early elimination phase while passive tumor targeting linearly decreased with a decrease in particle density. Moreover, lower‐density NPs are more easily distributed in the body and have shorter retention times in highly permeable organs than higher‐density NPs. The density‐dependent in vivo behavior of metal NPs likely results from their distinct margination in laminar blood flow, which opens up a new path for precise control of nanomedicines in vivo.