Renal Clearable Gold Nanoparticles Research Articles

Gold Nanoparticle Transport in the Injured Kidneys with Elevated Renal Function Biomarkers.

Renal function biomarkers such as serum blood urea nitrogen (BUN) and creatinine (Cr) serve as key indicators for guiding clinical decisions before administering kidney-excreted small-molecule agents. With engineered nanoparticles increasingly designed to be renally clearable to expedite their clinical translation, understanding the relationship between renal function biomarkers and nanoparticle transport in diseased kidneys becomes crucial to their biosafety in future clinical applications. In this study, renal-clearable gold nanoparticles (AuNPs) are used as X-ray contrast agents to noninvasively track their transport and retention in cisplatin-injured kidneys with varying BUN and Cr levels. The findings reveal that AuNP transport is significantly slowed in the medulla of severely injured kidneys, with BUN and Cr levels elevated to 10 times normal. In mildly injured kidneys, where BUN and Cr levels only four to five times higher than normal, AuNP transport and retention are not predictable by BUN and Cr levels but correlate strongly with the degree of tubular injury due to the formation of gold-protein casts in the Henle's loop of the medulla. These results underscore the need for caution when employing renal-clearable nanomedicines in compromised kidneys and highlight the potential of renal-clearable AuNPs as X-ray probes forassessing kidney injuries noninvasively.

Charge barriers in the kidney elimination of engineered nanoparticles

The renal elimination pathway is increasingly harnessed to reduce nonspecific accumulation of engineered nanoparticles within the body and expedite their clinical applications. While the size of nanoparticles is recognized as crucial for their passive filtration through the glomerulus due to its limited pore size, the influence of nanoparticle charge on their transport and interactions within the kidneys remains largely elusive. Herein, we report that the proximal tubule and peritubular capillary, rather than the glomerulus, serve as primary charge barriers to the transport of charged nanoparticles within the kidney. Employing a series of ultrasmall, renal-clearable gold nanoparticles (AuNPs) with precisely engineered surface charge characteristics as multimodal imaging agents, we have tracked their distribution and retention across various kidney components following intravenous administration. Our results reveal that retention in the proximal tubules is governed not by the nanoparticle's zeta-potential, but by direct Coulombic interactions between the positively charged surface ligands of the AuNPs and the negatively charged microvilli of proximal tubules. However, further enhancing these interactions leads to increased binding of the positively charged AuNPs to the peritubular capillaries during the initial phase of elimination, subsequently facilitating their slow passage through the glomeruli and interaction with tubular components in a charge-selective manner. By identifying these two critical charge-dependent barriers in the renal transport of nanoparticles, our findings offer a fundamental insight for the design of renal nanomedicines tailored for selective targeting within the kidney, laying down a foundation for developing targeting renal nanomedicines for future kidney disease management in the clinics.

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 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.