Abstract

With the rapid growth of the use of renal-clearable nanomedicines in disease targeting and therapy, a fundamental understanding of their injection dose responses is of great importance for future translation to clinical settings. Using glutathione-coated gold nanoparticles (GS-AuNPs) as a renal-clearable nanomedicine model for the construction of ultrasmall AuNPs with different serum protein binding abilities, we discover that the concentration-dependent serum protein binding capabilities endow GS-AuNPs with a more sensitive response to injection dose than NPs resistant to serum protein binding, resulting in greatly improved tumor-targeting efficiencies during both single and repeated low-dose injections; the performance is also distinct from nonrenal-clearable AuNPs coated with serum protein, which show decreased tumor-targeting efficiency with a decrease in the injection dose.

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