Browsing by Author "Xu, Jing"
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Item Interactions of Renal Clearable Gold Nanoparticles with the Kidneys in Vitro and in Vivo(2018-08) Xu, Jing; 0000-0001-6602-7335 (Xu, J); Zheng, JieThe emergence of renal clearable inorganic nanoparticles (NPs) offers a great opportunity to address the health concern raised by nonspecific accumulation of conventional inorganic NPs in the macrophage system, mostly in the liver and spleen. In recent decades, we have dedicated a remarkable amount of research in developing renal clearable gold nanoparticles (AuNPs) and investigating their biointeractions. Our group discovered that glutathione-coated renal clearable AuNPs (GS-AuNPs) can be efficiently excreted through the urinary system resulting in significantly reduced accumulation in the liver and spleen. By integrating the near-infrared fluorescence, GS-AuNPs can sensitively probe kidney clearance kinetics and indicate renal dysfunction. Future clinical translation requires a fundamental understanding of nano-bio interactions in the kidneys and the biocompatibility of GS-AuNPs. In this dissertation, Chapter 1 covers the status of renal clearable inorganic NPs and the current understanding of their biointeractions in the kidneys. Chapter 2 describes using X-ray imaging to visualize the transport of GS-AuNPs in the kidney components under both normal and pathological conditions. The unique deposition of GS-AuNPs in the diseased kidney offers a great chance to diagnose renal injury noninvasively. Chapter 3 focuses on the blood transport and biocompatibility of GS-AuNPs. The dose effect on the blood transport and renal clearance efficiency of GS-AuNPs is unraveled which results in high biocompatibility. Chapter 4 describes an in vitro study on the surface-ligand-density effect on interactions between GS-AuNPs and human kidney proximal tubular cells. The results demonstrate precise responses of proximal tubular cells to GS-AuNPs with different ligand densities in membrane affinity, cytotoxicity and the mechanism of cell death. Finally, a summary of the obtained understanding and future perspective are presented in Chapter 5.Item Physiological Stability and Renal Clearance of Ultrasmall Zwitterionic Gold Nanoparticles: Ligand Length Matters(American Institute of Physics, 2017-03-15) Ning, Xuhui; Peng, Chuanqi; Li, Eric S.; Xu, Jing; Vinluan, III,Rodrigo D.; Yu, Mengxiao; Zheng, Jie; 0000-0001-8546-1882 (Zheng, J); 22147423113244881679 (Zheng, J); Ning, Xuhui; Peng, Chuanqi; Li, Eric S.; Xu, Jing; Vinluan, III,Rodrigo D.; Yu, Mengxiao; Zheng, JieEfficient renal clearance has been observed from ultrasmall zwitterionic glutathione-coated gold nanoparticles (GS-AuNPs), which have broad preclinical applications in cancer diagnosis and kidney functional imaging. However, origin of such efficient renal clearance is still not clear. Herein, we conducted head-to-head comparison on physiological stability and renal clearance of two zwitterionic luminescent AuNPs coated with cysteine and glycine-cysteine (Cys-AuNPs and Gly-Cys-AuNPs), respectively. While both of them exhibited similar surface charges and the same core sizes, additional glycine slightly increased the hydrodynamic diameter of the AuNPs by 0.4 nm but significantly enhanced physiological stability of the AuNPs as well as altered their clearance pathways. These studies indicate that the ligand length, in addition to surface charges and size, also plays a key role in the physiological stability and renal clearance of ultrasmall zwitterionic inorganic NPs.Item Tuning the In Vivo Transport of Anticancer Drugs Using Renal-Clearable Gold Nanoparticles(Wiley-VCH Verlag, 2019-05-14) Peng, Chuanqi; Xu, Jing; Yu, Mengxiao; Ning, Xuhui; Huang, Yingyu; Du, Bujie; Hernandez, E.; Kapur, P.; Hsieh, J. -T; Zheng, Jie; 0000-0001-8546-1882 (Zheng, J); 22147423113244881679 (Zheng, J); Peng, Chuanqi; Xu, Jing; Yu, Mengxiao; Ning, Xuhui; Huang, Yingyu; Du, Bujie; Zheng, JiePrecise 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. © 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim