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Overshadowed by size\u2010, shape\u2010, and surface\u2010chemistry 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\u2010clearance efficiency exponentially increased in the early elimination phase while passive tumor targeting linearly decreased with a decrease in particle density. Moreover, lower\u2010density NPs are more easily distributed in the body and have shorter retention times in highly permeable organs than higher\u2010density NPs. 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