Tuning the In Vivo Transport of Anticancer Drugs Using Renal‐Clearable Gold Nanoparticles

Precise control of in vivo transport of anticancer drugs in normal and cancerous tissues with engineered nanoparticles is key to the future success of cancer nanomedicines in clinics. This requires a fundamental understanding of how engineered nanoparticles impact the targeting‐clearance and permeat...

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Veröffentlicht in:Angewandte Chemie International Edition 2019-06, Vol.58 (25), p.8479-8483
Hauptverfasser: Peng, Chuanqi, Xu, Jing, Yu, Mengxiao, Ning, Xuhui, Huang, Yingyu, Du, Bujie, Hernandez, Elizabeth, Kapur, Payal, Hsieh, Jer‐Tsong, Zheng, Jie
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Sprache:eng
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Zusammenfassung:Precise control of in vivo transport of anticancer drugs in normal and cancerous tissues with engineered nanoparticles is key to the future success of cancer nanomedicines in clinics. This requires a fundamental understanding of how engineered nanoparticles impact the targeting‐clearance and permeation‐retention paradoxes in the anticancer‐drug delivery. Herein, we systematically investigated how renal‐clearable gold nanoparticles (AuNPs) affect the permeation, distribution, and retention of the anticancer drug doxorubicin in both cancerous and normal tissues. Renal‐clearable AuNPs retain the advantages of the free drug, including rapid tumor targeting and high tumor vascular permeability. The renal‐clearable AuNPs also accelerated body clearance of off‐target drug via renal elimination. These results clearly indicate that diverse in vivo transport behaviors of engineered nanoparticles can be used to reconcile long‐standing paradoxes in the anticancer drug delivery. The best of both worlds: Long‐standing paradoxes in anticancer drug delivery, including high tumor targeting vs. rapid clearance, and high permeability vs. low systemic toxicity, can be addressed by using renal‐clearable gold nanoparticles (AuNPs). Doxorubicin‐loaded AuNPs (DOX@AuNPs) retain the rapid tumor targeting and high tumor permeability of the free drug, and off‐target DOX@AuNPs are more quickly cleared from the body than the free drug.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201903256