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ACS Nano. 2019 May 28;13(5):5720-5730. doi: 10.1021/acsnano.9b01154. Epub 2019 Apr 18.

Copper Sulfide Facilitates Hepatobiliary Clearance of Gold Nanoparticles through the Copper-Transporting ATPase ATP7B.

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Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy , The University of Rhode Island , Kingston , Rhode Island 02881 , United States.
Key Laboratory of Smart Drug Delivery, Ministry of Education, & State Key Laboratory of Molecular Engineering of Polymers, School of Pharmacy & Minhang Hospital , Fudan University , Shanghai 201203 , China.
James L. Winkle College of Pharmacy , University of Cincinnati , Cincinnati , Ohio 45221 , United States.


Metallic gold (Au) nanoparticles have great potential for a wide variety of biomedical applications. Yet, slow clearance of Au nanoparticles significantly hinders their clinical translation. Herein, we describe a strategy of utilizing the endogenous copper (Cu) clearance to improve the elimination of Au nanoparticles. Our mechanistic study reveals that a Cu-transporting P-type ATPase, ATP7B, mediates the exocytosis of CuS nanoparticles into bile canaliculi for their rapid hepatobiliary excretion. The efflux of CuS nanoparticles is adopted to facilitate the hepatobiliary clearance of Au nanoparticles through CuS-Au conjugation. Using two different CuS-Au nanoconjugates, we demonstrate that CuS increases the biliary Au excretion of CuS-Au nanospheres or CuS-Au nanorods in mice or rats in comparison to that of their respective unconjugated Au nanoparticles postintravenous injection. The current CuS-Au conjugation approach provides a feasible strategy to enhance the hepatobiliary clearance of Au nanoparticles that may be applicable to various structures.


ATP7B; copper sulfide nanoparticle; gold nanoparticle; hepatobiliary excretion; nanoconjugate


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