Design considerations for tumour-targeted nanoparticles

TLDR: This study shows that quantum dots functionalized with high-affinity small-molecule ligands that target tumours can also be cleared by the kidneys if their hydrodynamic diameter is less than this value, which sets an upper limit of 5-10 ligands per quantum dot for renal clearance.

Abstract: Inorganic/organic hybrid nanoparticles are potentially useful in biomedicine, but to avoid non-specific background fluorescence and long-term toxicity, they need to be cleared from the body within a reasonable timescale 1 . Previously, we have shown that rigid spherical nanoparticles such as quantum dots can be cleared by the kidneys if they have a hydrodynamic diameter of approximately 5.5 nm and a zwitterionic surface charge 2 . Here, we show that quantum dots functionalized with highaffinity small-molecule ligands that target tumours can also be cleared by the kidneys if their hydrodynamic diameter is less than this value, which sets an upper limit of 5–10 ligands per quantum dot for renal clearance. Animal models of prostate cancer and melanoma show receptor-specific imaging and renal clearance within 4 h post-injection. This study suggests a set of design rules for the clinical translation of targeted nanoparticles that can be eliminated through the kidneys. Although many classes of biocompatible, inorganic-based nanomaterials have been developed for medical diagnostics and therapeutics 3–7 , many presently available formulations require potentially toxic elements 8 . Efforts have been made to reduce toxicity by modulating the composition, particle shape, physical size and surface coating of the nanoparticles 9 . One common strategy is to engineer nanoparticles using biocompatible and biodegradable polymeric coatings 10–13 . However, polymer coatings generally increase particle