Browsing by Author "Peng, Chuanqi"
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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 Renal-Clearable Gold Nanoparticle-Based Drug Delivery Systems(2019-07-19) Peng, Chuanqi; Zheng, JieEngineered nanoparticles (NPs) have demonstrated unprecedented physiological understandings and versatile biomedical applications. However, clinical translation of cancer nanomedicines remains slow due to limited tumor targeting but elevated body retention of off-target therapeutics. With decreased size and surface passivation, the engineered, ultrasmall NPs have shown not only efficient body elimination through renal pathway, but also high targeting efficiency to the disease tissues as tumors. Therefore, such renal-clearable NPs could possibly address the many challenges faced by non-renal-clearable nanocarriers, once the efficient and stable drug loading as well as systematic physiological understandings of such ultrasmall delivery systems were achieved. In Chapter 1, we prepared the delivery vector by using the renal-clearable gold nanoparticles (AuNPs) with high tumor targeting efficiency. By rational design and modification, we firstly loaded the widely used anticancer drug, doxorubicin (DOX), on the renal-clearable AuNPs at high loading capacity, and then investigated the physiological stability, drug release and in vitro cytotoxicity studies. In addition, this ultrasmall AuNPs can also load many other small-molecule therapeutic or imaging agents as well as small-interfering RNAs for gene therapy. In Chapter 2 and 3, we systematically investigated blood circulation, tumor targeting, intratumoral transport, as well as body elimination of the renal-clearable 5-nm AuNP-based drug delivery system (DDS). The renal-clearable DDS not only significantly enhanced delivery efficiency and intratumoral transport of drug but also accelerated the renal clearance and body elimination of offtarget drug compared to both free drug (DOX) and the non-renal-clearable 30-nm DDS. As a result, the therapeutic index was improved by both enhanced efficacy and safety. In Chapter 4, we investigated the targeting and imaging of poorly permeable brain tumors (gliomas) by using the renal-clearable zwitterionic 3-nm AuNPs. The renal-clearable AuNPs increased tumor targeting efficiency and specificity compared to non-renal-clearable 18-nm counterpart. The effective NP penetration in brain tumorssuggeststhat renal-clearable AuNPs may achieve early brain tumor detection once integrated with nuclear imaging techniques used in the clinics. In Chapter 5, we investigated the ligand-directed in situ growth of AuNPs in biological tissues and the possible biological interaction of biomolecules. The results indicate that the ligand-directed AuNP growth can serve as a novel tool for tissue imaging via nanoparticle labeling with multimodality and multi-scale characterization. Herein, we not only report the design and practice of renal-clearable AuNP-based DDS as well as tissue targeting and imaging with AuNPs, we also conclude the outlook and future work for the renal-clearable AuNPs. We believe the renal-clearable AuNPs can shift the paradigm in drug delivery and expedite the clinical translation of cancer nanomedicines once some critical challenges are further addressed in the near future.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