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Biodegradable Gold Nanoclusters with Improved Excretion Due to pH-Triggered Hydrophobic-to-Hydrophilic Transition.

ABSTRACT: Gold is a highly useful nanomaterial for many clinical applications, but its poor biodegradability can impair long-term physiological clearance. Large gold nanoparticles (∼10-200 nm), such as those required for long blood circulation times and appreciable tumor localization, often exhibit little to no dissolution and excretion. This can be improved by incorporating small gold particles within a larger entity, but elimination may still be protracted due to incomplete dispersion of gold. The present study describes a novel gold nanoparticle formulation capable of environmentally triggered decomposition. Ultrasmall gold nanoparticles are coated with thiolated dextran, and hydrophobic acetal groups are installed through direct covalent modification of the dextran. This hydrophobic exterior allows gold to be densely packed within ∼150 nm polymeric micelles. Upon exposure to an acidic environment, the acetal groups are cleaved and the gold nanoparticles become highly water-soluble, leading to destabilization of the micelle. Within 24 h, the ultrasmall water-soluble gold particles are released from the micelle and readily dispersed. Micelle degradation and gold nanoparticle dispersion was imaged in cultured macrophages, and micelle-treated mice displayed progressive physiological clearance of gold, with >85% elimination from the liver over three months. These particles present a novel nanomaterial formulation and address a critical unresolved barrier for clinical translation of gold nanoparticles.

PROVIDER: S-EPMC7238296 | BioStudies |

REPOSITORIES: biostudies

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