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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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Antibiotic Bone Cement and Ultraviolet Light Use in Total Knee Arthroplasty

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Open Journal of Orthopedics 2016年第9期6卷 283-293页

作者： John B. Meding kenneth e. Davis Merrill A. Ritter The Center for Hip and Knee Surgery St. Francis Hospital Mooresville Mooresville Indiana USA

Objective: The purpose of this study was to determine usefulness of antibiotic bone cement and UV light in primary Total Knee Arthroplasty (TKA). Patients and Methods: Between 1986 and 2008, 3105 TKAs were performed using 750 mg of cefuroxime per bag of cement (Group 1), 7537 using cefuroxime and UV light (Group 2), and 4573 using UV light and gentamicin premixed (Group 3). Results: The primary infection rate was 0.57% (87 acute postoperative infections). Of these, 27 (0.9%) were in Group 1, 44 (0.6%) were in Group 2, and 16 (0.35%) were in Group 3 (p = 0.0013). Kaplan-Meier survival in Groups 1 - 3 for reoperation for aseptic loosening of any component at 5 years was 0.9908, 0.9927, and 0.9959, respectively (p = 0.1315). Conclusion: Despite potential concerns mentioned in the literature, these results continue to support the use of antibiotic bone cement and UV lights during TKA.

关键词： Antibiotic Bone Cement Ultraviolet Light Total Knee Arthroplasty Infection Complications

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evaluation of a Rapid Immunochromatographic Middle east Respiratory Syndrome Coronavirus Antigen Detection Assay

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Infectious Microbes & Diseases 2022年第4期4卷 175-177页

作者： Susanna Kar-Pui Lau kenneth Sze-Ming Li Jade Lee-Lee Teng Sunitha Joseph Hayes Kam-Hei Luk Joshua Fung Ulrich Wernery Patrick Chiu-Yat Woo Department of Microbiology School of Clinical MedicineLi Ka Shing Faculty of MedicineThe University of Hong KongPokfulamHong KongChina Central Veterinary Research Laboratory DubaiUnited Arab Emirates PhD Program in Translational Medicine and Department of Life Sciences National Chung Hsing UniversityTaichungTaiwan The ieGG and Animal Biotechnology Research Center National Chung Hsing UniversityTaichungTaiwan

Middle east respiratory syndrome coronavirus(MeRS-CoV)infection in humans has a high mortality of>30%.Dromedaries are the reservoir of MeRS-CoV and the main source of human ***,MeRS-CoV infections in dromedaries are usually *** diagnosis of MeRS-CoV infection in these animals is important in preventing camel-to-human transmission of the *** possible cross-reactivity of a previously reported rapid nucleocapsid protein-based antigen detection assay for MeRS-CoV was examined with different CoVs,including Tylonycteris bat CoV HKU4,dromedary camel CoV UAe-HKU23,human CoV-229e,human CoV-OC43,severe acute respiratory syndrome CoV-2 and rabbit CoV HKU14,where none of them showed false-positive *** assay was further validated using quantitative real-time reverse transcription-polymerase chain reaction-confirmed MeRS-CoV-positive and MeRS-CoV-negative dromedary nasal samples collected in Dubai,the United Arab emirates,which showed that the rapid antigen detection assay has a specificity of 100%and sensitivity of 91.7%.

关键词： MeRS-CoV rapid antigen detection assay dromedary camels

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Advanced therapy in cardiac surgery / 2nd ed.

Advanced therapy in cardiac surgery /

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2003年

作者： Franco kenneth L.

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Therapy decisions for the symptomatic patient wil metastatic castration-resistant prostate cancer

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Asian Journal of Andrology 2015年第6期17卷 936-938,I0008页

作者： Mark C Markowski kenneth J Pienta Johns Hopkins University School of Medicine Baltimore MD 21287 USA.

Metastatic prostate cancer continues to kill approximately 30,000 men per year. Since 2010, five new therapeutic agents have been Food and Drug Administration （FDA） approved to treat metastatic castration-resistant prostate cancer （mCRPC）. With the increasingnumber of therapies available to clinicians, the most effective sequence in which to implement these treatments remains unknown. The presence or absence of symptoms （i.e., bony pain, visceral crisis） is a key parameter that informs the decision-making process regarding therapy. Treatment algorithms based on： 1） asymptomatic/minimal symptoms, 2） moderate symptoms or chemotherapy ineligible or 3） symptomatic disease need to be developed.

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efficacy Improvement of a Bioherbicidal Fungus Using a Formulation-Based Approach

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American Journal of Plant Sciences 2016年第16期7卷 2349-2358页

作者： Clyde D. Boyette Robert e. Hoagland kenneth C. Stetina USDA-ARS Biological Control of Pests Research Unit Stoneville MS USA USDA-ARS Crop Production Systems Research Unit Stoneville MS USA

Greenhouse experiments were conducted to determine the effects of an invert (water-in-oil) emulsion (Ie) on dew period duration and dew delay of Colletotrichum coccodes for biocontrol of the problematic weed, eastern black nightshade (Solanum ptycanthum). Dew periods of 4, 8, or 12 h provided 10%, 25%, and 40% control of eastern black nightshade plants, respectively, when C. coccodes (Strain NRRL 15,547) spores were applied in water + Tween 80 surfactant 12 days after inoculation, but a minimum of 16 h of dew was required to achieve ~95% plant mortality. In contrast, at these same intervals of dew, 95%, 100% and 100% mortality occurred, respectively, when fungal spores were formulated in the Ie. even in the absence of dew, 60% mortality and 70% dry weight reductions of plants was achieved with the fungus/Ie formulation Delaying dew by 2 h after inoculation did not significantly reduce weed control or plant dry weight reductions when plants were inoculated with the fungus either in the aqueous or in the Ie formulation. However, when dew was delayed for 4, 8, or 12 h, only 60%, 50%, and 25% mortality, respectively, of plants receiving the aqueous spore treatment occurred. In contrast, 95%, 90%, and 90% weed mortality occurred after the same dew delays of plants receiving the fungus/ Ie treatments. These results demonstrate that formulating C. coccodes spores in an invert emulsion greatly improves the bioherbicidal potential of this fungus. Furthermore, results suggest that this formulation may render pathogens previously rejected for development as bioherbicides due to restrictive dew requirements more efficacious for use in controlling their target weeds.

关键词： Colletotrichum coccodes Solanum ptycanthum Bioherbicide Invert emulsion Formulation

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系统分析与设计

系统分析与设计

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作者： (美)肯尼斯·e. 肯德尔(kenneth e. Kendall)，(美)朱莉·e. 肯德尔(Julie e. Kendall)

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Fluorescence Intensity Decay Shape Analysis Microscopy （FIDSAM） for Quantitative and Sensitive Live-Cell Imaging： A Novel Technique for Fluorescence Microscopy of endogenously expressed Fusion-Proteins

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Molecular Plant 2010年第3期3卷 555-562页

作者： Frank Schleifenbaum Kirstin elgass Marcus Sackrow Katharina Caesar kenneth Berendzen Alfred J. Meixner Klaus Hatter Center for Plant Molecular Biology Department of Plant Physiology University of Tubingen Auf der Morgenstelle 1 72076 Tubingen Germany Institute of Physical and Theoretical Chemistry University of Tubingen Auf der Morgenstelle 8 72076 Tubingen Germany

Fluorescent studies of living plant cells such as confocal microscopy and fluorescence lifetime imaging often suffer from a strong autofluorescent background contribution that significantly reduces the dynamic image contrast and the quantitative access to sub-cellular processes at high spatial resolution. Here, we present a novel technique--fluorescence intensity decay shape analysis microscopy （FIDSAM） to enhance the dynamic contrast of a fluorescence image of at least one order of magnitude. The method is based on the analysis of the shape of the fluorescence intensity decay （fluorescence lifetime curve） and benefits from the fact that the decay patterns of typical fluorescence label dyes strongly differ from emission decay curves of autofluorescent sample areas. Using FIDSAM, we investigated Arabidopsis thaliana hypocotyl cells in their tissue environment, which accumulate an eGFP fusion of the plasma membrane marker protein LTI6b （LTI6b-eGFP） to low level. Whereas in conventional confocal fluorescence images, the membranes of neighboring cells can hardly be optically resolved due to the strong autofluorescence of the cell wall, FIDSAM allows for imaging of single, isolated membranes at high spatial resolution. Thus, FIDSAM will enable the sub-cellular analysis of even low-expressed fluorophoretagged proteins in living plant cells. Furthermore, the combination of FIDSAM with fluorescence lifetime imaging provides the basis to study the local physico-chemical environment of fluorophore-tagged biomolecules in living plant cells.

关键词： Cell structure cell walls membrane proteins high-resolution fluorescence microscopy.

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General chemistry kenneth W. Whitten ... [et al.]. 7th ed.

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2004年

作者： kenneth W. Whitten ... [et al.].

2 CD ROMS in pocket inside front cover.

ISBN: (纸本)9780534408602

2 CD ROMS in pocket inside front cover.

关键词： Chemistry.

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Transportation of AIe-visualized nanoliposomes is dominated by the protein corona

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National Science Review 2021年第6期8卷 23-33页

作者： Yi-Feng Wang Chunqiu Zhang Keni Yang Yufei Wang Shaobo Shan Yan Yan kenneth A.Dawson Chen Wang Xing-Jie Liang CAS Key Laboratory for Biomedical effects of Nanomaterials and Nanosafety CAS Center for Excellence in NanoscienceNational Center for Nanoscience and Technology of China University of Chinese Academy of Sciences State Key Laboratory of Medicinal Chemical Biology Key Laboratory of Bioactive Materials of Ministry of Educationand College of Life SciencesNankai University Centre for Bio Nano Interactions School of ChemistryUniversity College Dublin School of Biomolecular and Biomedical Science University College Dublin Guangdong Provincial education Department Key Laboratory of Nano-Immuno-regulation Tumor Microenvironment The Second Affiliated HospitalGuangzhou Medical University

Liposomes, especially cationic liposomes, are the most common and well-investigated nanocarriers for biomedical applications, such as drug and gene delivery. Like other types of nanomaterials, once liposomes are incubated in a biological milieu, their surface can be immediately cloaked by biological components to form a protein corona, which confers a new ‘biological identity’ and modulates downstream interactions with cells. However, it remains unclear how the protein corona affects the transportation mechanism after liposomes interact with cells. Here, we employed home-made aggregation-induced-emission-visualized nanoliposomes TR4@Lipo as a model to investigate transportation with or without the protein corona by optical imaging techniques. The results show that the protein corona can change the cellular transportation mechanism of TR4@Lipo from energy-independent membrane fusion to energy-dependent *** protein corona also modulates the intracellular distribution of loaded cargoes. This knowledge furthers our understanding of bio-nano interactions and is important for the efficient use of cationic liposomes.

关键词： aggregation-induced emission (AIe) cationic liposomes protein corona endocytosis membrane fusion

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