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Design and in vivo characterization of kidney-targeting multimodal micelles for renal drug delivery

Nano Research 2018年第10期11卷 5584-5595页

作者： Jonathan Wang christopher poon Deborah Chin Sarah Milkowski Vivian Lu Kenneth R. Hallows Eun Ji Chung Department of Biomedical Engineering University of Southern California Los Angeles CA 90089 USA Division of Nephrology and Hypertension Department of Medicine Keck School of Medicine University of Southern California Los Angeles CA 90033 USA USC/UKRO Kidney Research Center Keck School of Medicine University of Southern California Los Angeles CA 90033 USA Norris Comprehensive Cancer Center University of Southern California Los Angeles CA 90033 USA Department of Stem Cell Biology and Regenerative Medicine University of Southern California Los Angeles CA 90033 USA Mork Family Department of Chemical Engineering and Materials Science University of Southern California Los Angeles CA 90089 USA

One in three Americans is at risk for developing chronic kidney disease （CKD） and end-stage renal disease （ESRD）, leading to the need for dialysis or a kidney transplant. Small-molecule drugs have been proposed as therapies to manage kidney diseases, but high dosages are often required to achieve therapeutic efficacy, generating off-target side effects, some of which are lethal. To address these limitations, we developed a novel kidney-targeting multimodal micelle （KM） system for drug delivery applications. SpecificaU~ we incorporated the kidney-targeting peptide （Lysine-Lysine-Glutamic acid-Glutamic acid-Glutamic acid）3-Lysine）（（KKEEE）3K） into micelles. This peptide binds to megalin, a multi-ligand cell surface receptor present on renal tubule cells. When incubated with human kidney proximal tubule cells, KMs were found to be biocompatible in vitro. In vivo, KMs showed higher accumulation in the kidneys as compared to a non-targeted （NT） control upon intravenous injection in wild-type C57BL/6J mice. Histological evaluation showed no signs of tissue damage, while blood urea nitrogen （BUN） and creatinine levels were within normal ranges, validating the preservation of kidney health upon micelle administration. To our knowledge, this is the first utilization of （KKEEE）BK in a nanoparticle formulation, and our study offers strong evidence that this novel nanoparticle platform can be used as a candidate drug delivery carrier to direct therapeutics to diseased tissue in CKD.

关键词： micelle kidney disease renal targeting biodistribution nanoparticle

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Repair of traumatic plasmalemmal damage to neurons and other eukaryotic cells

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Neural Regeneration Research 2016年第7期11卷 1033-1042页

作者： George D.Bittner christopher S.Spaeth Andrew D.poon Zachary S.Burgess christopher H.Mc Gill Department of Neuroscience The University of Texas at Austin

The repair（sealing） of plasmalemmal damage,consisting of small holes to complete transections,is critical for cell survival,especially for neurons that rarely regenerate cell *** first describe and evaluate different measures of cell *** measures,including morphological/ultra-structural observations,membrane potential,and input resistance,provide very ambiguous assessments of plasmalemmal *** contrast,measures of ionic current flow and dye barriers can,if appropriately used,provide more accurate *** describe the effects of various substances（calcium,calpains,cytoskeletal proteins,ESCRT proteins,m UNC-13,NSF,PEG） and biochemical pathways（PKA,PKC,PLC,Epac,cytosolic oxidation） on plasmalemmal sealing probability,and suggest that substances,pathways,and cellular events associated with plasmalemmal sealing have undergone a very conservative *** sealing,calcium ion influx mobilizes vesicles and other membranous structures（lysosomes,mitochondria,etc.） in a continuous fashion to form a vesicular plug that gradually restricts diffusion of increasingly smaller molecules and ions over a period of seconds to ***,we find no direct evidence that sealing occurs through the collapse and fusion of severed plasmalemmal leaflets,or in a single step involving the fusion of one large wound vesicle with the nearby,undamaged *** describe how increases in perikaryal calcium levels following axonal transection account for observations that cell body survival decreases the closer an axon is transected to the ***,we speculate on relationships between plasmalemmal sealing,Wallerian degeneration,and the ability of polyethylene glycol（PEG） to seal cell membranes and rejoin severed axonal ends – an important consideration for the future treatment of trauma to peripheral nerves.A better knowledge of biochemical pathways and cytoplasmic structures involved in plasmalemmal sealing might provide insights to develo

关键词： sealing traumatic eukaryotic vesicles axonal membranous closer biochemical vesicular muscular

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金融行为监管局和审慎监管局的设立:不仅仅是结构转变?

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公司法律评论 2014年第1期 242-257页

作者：薛晟(译) Helen Marshall christopher Leonard Rosemarie Paul Ezra Zahabi Chris poon Cecile Chastre Jessica Howlett 不详

引言2013年是加强监管的一年。在一系列政策颁布之后,2013年内金融监管的格局发生了巨大的变化。英国撤销了金融服务管理局,设立了审慎监管局和金融行为监管局。在本次合规专员公告中,我们研究得出,新监管机构的设立将对金融监管方式产... 详细信息

引言2013年是加强监管的一年。在一系列政策颁布之后,2013年内金融监管的格局发生了巨大的变化。英国撤销了金融服务管理局,设立了审慎监管局和金融行为监管局。在本次合规专员公告中,我们研究得出,新监管机构的设立将对金融监管方式产生重要影响。监管部门似乎决定建立新的监管形式.

关键词：金融英国影响专员利益合规监管监管局

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