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1. 发明授权

US08883519B1 Oxidase activity of polymeric coated cerium oxide nanoparticles 有权
标题翻译：聚合物涂覆的氧化铈纳米粒子的氧化酶活性
公开(公告)号：US08883519B1
公开(公告)日：2014-11-11
申请号：US12704678
申请日：2010-02-12
申请人： J. Manuel Perez , Atul Asati , Santimukul Santra , Charalambos Kaittanis , Sudip Nath
发明人： J. Manuel Perez , Atul Asati , Santimukul Santra , Charalambos Kaittanis , Sudip Nath
IPC分类号： G01N33/553 , G01N33/543
CPC分类号： G01N33/9413 , B82Y15/00 , G01N33/5432
摘要： Methods, systems, compositions include biocompatible polymer coated nanoceria that function as aqueous redox catalyst with enhanced activity at an acidic to moderately alkaline pH value between 1 and 8. The compositions are used as oxidizing agents for decomposition, decontamination or inactivation of organic contaminants, such as, pesticides and chemical warfare agents. Another use includes nanoceria as targetable nanocatalyst prepared by conjugating various targeting ligands to the nanoparticle coating to form a colorimetric or fluorescent probe in immunoassays and other molecule binding assays that involve the use of a molecule in solution that changes the color of the solution or emits a fluorescent signal, where localization of nanoceria to organs or tissue is assessed by treatment with an oxidation sensitive dye or other detection devices. Versatility and uses of the nanoceria compositions are controlled by pH value, choice of dye substrate and thickness of the polymer coating on the ceria nanoparticles.
摘要翻译：方法，系统，组合物包括在1至8之间的酸性至中等碱性pH值下具有增强活性的作为水性氧化还原催化剂的生物相容性聚合物包衣纳米片。该组合物用作有机污染物的分解，去污或灭活的氧化剂，作为农药和化学战剂。另一种用途包括将纳米囊作为可靶向的纳米催化剂，其通过将各种靶向配体与纳米颗粒涂层结合而形成可靶向的纳米催化剂，以在免疫测定和其它分子结合测定中形成比色或荧光探针，其涉及使用溶液中的分子，其改变溶液的颜色或发射荧光信号，其中通过用氧化敏感染料或其他检测装置处理来评估纳米器官对器官或组织的定位。通过pH值，染料底物的选择和二氧化铈纳米粒子上聚合物涂层的厚度来控制纳米材料组合物的多功能性和用途。

2. 发明授权

US08795733B1 Cerium-oxide nanoparticle based device for the detection of reactive oxygen species and monitoring of chronic inflammation 有权
标题翻译：基于氧化铈纳米颗粒的器件，用于检测活性氧物质和监测慢性炎症
公开(公告)号：US08795733B1
公开(公告)日：2014-08-05
申请号：US13602611
申请日：2012-09-04
申请人： Jesus Manuel Perez , Charalambos Kaittanis , Atul Asati , Santimukul Santra
发明人： Jesus Manuel Perez , Charalambos Kaittanis , Atul Asati , Santimukul Santra
IPC分类号： A61K9/14
CPC分类号： A61K49/0093 , A61K49/0004 , A61K49/0054 , A61K49/1854 , A61K49/1857 , A61K49/1863
摘要： A polymer-coated cerium oxide based device and system is disclosed for detecting reactive oxygen species and monitoring chronic inflammation. The device and system encapsulate free therapeutic nanoparticle elements not present in a living body in a prosthetic or implantable unit. Embodiment one is a two-chamber structure with a reactive oxygen species (ROS) scavenging component on one end and at the opposite end is an imaging agent consisting of at least one of a fluorophore capable of fluorescence emission, a chemiluminescent agent, a magnetic relaxation agent and an X-ray contrast agent. Embodiment two is a single chamber device consisting of a multifunctional nanocomposite with a ROS-scavenging nanoparticle constituent (nanoceria) and a multimodal reporting nanoparticle component (i.e. Dex-IO-DiR). The device and system are utilized in treatment of diseases with a pro-inflammatory component, including, but not limited to, Crohn's disease, ulcerative colitis, inflammatory bowel disease, cystic fibrosis, arthritis, and cancer chemotherapy.
摘要翻译：公开了一种用于检测活性氧物质并监测慢性炎症的聚合物涂覆的氧化铈基装置和系统。该装置和系统封装在假体或可植入单元中不存在于生物体中的游离的治疗性纳米颗粒元件。实施方案一是在一端具有活性氧（ROS）清除组分的两室结构，相对端是由能够发荧光的荧光团，化学发光剂，磁弛豫中的至少一种构成的成像剂药剂和X射线造影剂。实施方案二是由具有ROS清除纳米颗粒组分（纳米碳）和多峰报告纳米颗粒组分（即Dex-IO-DiR）的多功能纳米复合材料组成的单室装置。该装置和系统用于治疗具有促炎成分的疾病，包括但不限于克罗恩病，溃疡性结肠炎，炎症性肠病，囊性纤维化，关节炎和癌症化疗。

3. 发明授权

US08795731B1 Cerium oxide nanoparticle-based device for the detection of reactive oxygen species and monitoring of chronic inflammation 有权
标题翻译：基于氧化铈纳米粒子的器件，用于检测活性氧物质和监测慢性炎症
公开(公告)号：US08795731B1
公开(公告)日：2014-08-05
申请号：US12924976
申请日：2010-10-08
申请人： Jesus Manuel Perez , Charalambos Kaittanis , Atul Asati , Santimukul Santra
发明人： Jesus Manuel Perez , Charalambos Kaittanis , Atul Asati , Santimukul Santra
IPC分类号： A61K9/14
CPC分类号： A61K49/0019 , A61B5/411 , A61B5/686 , A61K9/0024 , A61K9/5138 , A61K45/06 , A61K49/0032 , A61K49/0034
摘要： A polymer-coated cerium oxide based device and system is disclosed for detecting reactive oxygen species and monitoring chronic inflammation. The device and system encapsulate free therapeutic nanoparticle elements not present in a living body in a prosthetic or implantable unit. Embodiment one is a two-chamber structure with a reactive oxygen species (ROS) scavenging component on one end and at the opposite end is an imaging agent consisting of at least one of a fluorophore capable of fluorescence emission, a chemiluminescent agent, a magnetic relaxation agent and an X-ray contrast agent. Embodiment two is a single chamber device consisting of a multifunctional nanocomposite with a ROS-scavenging nanoparticle constituent (nanoceria) and a multimodal reporting nanoparticle component (i.e. Dex-IO-DiR). The device and system are utilized in treatment of diseases with a pro-inflammatory component, including, but not limited to, Crohn's disease, ulcerative colitis, inflammatory bowel disease, cystic fibrosis, arthritis, and cancer chemotherapy.
摘要翻译：公开了一种用于检测活性氧物质并监测慢性炎症的聚合物涂覆的氧化铈基装置和系统。该装置和系统封装在假体或可植入单元中不存在于生物体中的游离的治疗性纳米颗粒元件。实施方案一是在一端具有活性氧（ROS）清除组分的两室结构，相对端是由能够发荧光的荧光团，化学发光剂，磁弛豫中的至少一种构成的成像剂药剂和X射线造影剂。实施方案二是由具有ROS清除纳米颗粒组分（纳米碳）和多峰报告纳米颗粒组分（即Dex-IO-DiR）的多功能纳米复合材料组成的单室装置。该装置和系统用于治疗具有促炎成分的疾病，包括但不限于克罗恩病，溃疡性结肠炎，炎症性肠病，囊性纤维化，关节炎和癌症化疗。

4. 发明授权

US10213458B2 Differential tumor cell cytotoxicity via contact with coated cerium oxide nanoparticles 有权
公开(公告)号：US10213458B2
公开(公告)日：2019-02-26
申请号：US14862548
申请日：2015-09-23
申请人： Jesus Manuel Perez , Atul Asati , Santimukul Santra , Charalambos Kaittanis
发明人： Jesus Manuel Perez , Atul Asati , Santimukul Santra , Charalambos Kaittanis
IPC分类号： A61K9/50 , A61K33/24 , A61K9/51
摘要： Differential surface-charge-dependent localization of nanoceria in normal cells and cancer cells plays a critical role in the toxicity profile of a nanoceria particle. Engineered surface-coated cerium oxide nanoparticles with different surface charges that are positive, negative and neutral provide therapeutic results for normal and cancer cell lines. Results show that nanoceria with a positive or neutral charge enters most of the cell lines studied, while nanoceria with a negative charge internalizes mostly in the cancer cell lines. Moreover, upon entry into the cells, nanoceria is localized to different cell compartments (e.g. cytoplasm and lysosomes) depending on the nanoparticle surface charge. The internalization and subcellular localization of nanoceria plays a key role in the nanoparticle cytotoxicity profile, exhibiting significant toxicity when they localize in the lysosomes of the cancer cell lines. In contrast, minimal toxicity is observed when they localize into the cytoplasm or do not enter the cells.

5. 发明申请

US20160074334A1 Differential Tumor Cell Cytotoxicity Via Contact With Coated Cerium Oxide Nanoparticles 审中-公开
标题翻译：通过与涂覆的氧化铈纳米颗粒接触的差异肿瘤细胞的细胞毒性
公开(公告)号：US20160074334A1
公开(公告)日：2016-03-17
申请号：US14862548
申请日：2015-09-23
申请人： Jesus Manuel Perez , Atul Asati , Santimukul Santra , Charalambos Kaittanis
发明人： Jesus Manuel Perez , Atul Asati , Santimukul Santra , Charalambos Kaittanis
IPC分类号： A61K9/50 , A61K33/24
CPC分类号： A61K33/24 , A61K9/5138 , A61K9/5161
摘要： Differential surface-charge-dependent localization of nanoceria in normal cells and cancer cells plays a critical role in the toxicity profile of a nanoceria particle. Engineered surface-coated cerium oxide nanoparticles with different surface charges that are positive, negative and neutral provide therapeutic results for normal and cancer cell lines. Results show that nanoceria with a positive or neutral charge enters most of the cell lines studied, while nanoceria with a negative charge internalizes mostly in the cancer cell lines. Moreover, upon entry into the cells, nanoceria is localized to different cell compartments (e.g. cytoplasm and lysosomes) depending on the nanoparticle surface charge. The internalization and subcellular localization of nanoceria plays a key role in the nanoparticle cytotoxicity profile, exhibiting significant toxicity when they localize in the lysosomes of the cancer cell lines. In contrast, minimal toxicity is observed when they localize into the cytoplasm or do not enter the cells.
摘要翻译：正常细胞和癌细胞中纳米囊的差异表面电荷依赖性定位在纳米颗粒的毒性特征中起关键作用。具有正，负和中性的不同表面电荷的工程表面包覆的氧化铈纳米颗粒为正常和癌细胞系提供治疗结果。结果表明，具有阳性或中性电荷的纳米药物进入研究的大部分细胞系，而具有负电荷的纳米药物主要在癌细胞系中内化。此外，在进入细胞后，根据纳米颗粒的表面电荷，将纳米片定位于不同的细胞区室（例如细胞质和溶酶体）。纳米颗粒的内化和亚细胞定位在纳米颗粒细胞毒性谱中起关键作用，当它们定位在癌细胞系的溶酶体中时显示出显着的毒性。相比之下，当它们定位到细胞质中或不进入细胞时，观察到最小的毒性。

6. 发明申请

US20160074434A1 Application Device for Inducing Cytotoxicity to Tumor Cells Via Coated Cerium Oxide Nanoparticles 审中-公开
标题翻译：通过涂覆的氧化铈纳米颗粒诱导肿瘤细胞的细胞毒性的应用装置
公开(公告)号：US20160074434A1
公开(公告)日：2016-03-17
申请号：US14862559
申请日：2015-09-23
申请人： Jesus Manuel Perez , Atul Asati , Santimukul Santra , Charalambos Kaittanis
发明人： Jesus Manuel Perez , Atul Asati , Santimukul Santra , Charalambos Kaittanis
IPC分类号： A61K33/24 , A61K9/50
CPC分类号： A61K33/24 , A61K9/5138 , A61K9/5161
摘要： Differential surface-charge-dependent localization of nanoceria in normal cells and cancer cells plays a critical role in the toxicity profile of a nanoceria particle. Engineered surface-coated cerium oxide nanoparticles with different surface charges that are positive, negative and neutral provide therapeutic results for normal and cancer cell lines. Results show that nanoceria with a positive or neutral charge enters most of the cell lines studied, while nanoceria with a negative charge internalizes mostly in the cancer cell lines. Moreover, upon entry into the cells, nanoceria is localized to different cell compartments (e.g. cytoplasm and lysosomes) depending on the nanoparticle surface charge. The internalization and subcellular localization of nanoceria plays a key role in the nanoparticle cytotoxicity profile, exhibiting significant toxicity when they localize in the lysosomes of the cancer cell lines. In contrast, minimal toxicity is observed when they localize into the cytoplasm or do not enter the cells.
摘要翻译：正常细胞和癌细胞中纳米囊的差异表面电荷依赖性定位在纳米颗粒的毒性特征中起关键作用。具有正，负和中性的不同表面电荷的工程表面包覆的氧化铈纳米颗粒为正常和癌细胞系提供治疗结果。结果表明，具有阳性或中性电荷的纳米药物进入研究的大部分细胞系，而具有负电荷的纳米药物主要在癌细胞系中内化。此外，在进入细胞后，根据纳米颗粒的表面电荷，将纳米片定位于不同的细胞区室（例如细胞质和溶酶体）。纳米颗粒的内化和亚细胞定位在纳米颗粒细胞毒性谱中起关键作用，当它们定位在癌细胞系的溶酶体中时显示出显着的毒性。相比之下，当它们定位到细胞质中或不进入细胞时，观察到最小的毒性。

7. 发明授权

US09119391B1 Polymer coated ceria nanoparticles for selective cytoprotection 有权
标题翻译：用于选择性细胞保护的聚合物包被的二氧化铈纳米颗粒
公开(公告)号：US09119391B1
公开(公告)日：2015-09-01
申请号：US12169179
申请日：2008-07-08
申请人： Jesus Manuel Perez , Atul Asati , Sudip Nath , Charalambos Kaittanis
发明人： Jesus Manuel Perez , Atul Asati , Sudip Nath , Charalambos Kaittanis
IPC分类号： A01N59/16 , A61K9/14 , A01N1/02
CPC分类号： A01N1/02 , A61K9/5161 , A61K33/00
摘要： Methods, systems and compositions are disclosed wherein normal, non-transformed, healthy biological cells are protected from oxidative stress, radiation therapy and chemotherapy while diseased, transformed cells, such as, cancer cells, are provided no protection by the biocompatible, polymer coated nanoceria composition of the present invention. The polymer-coated nanoceria preparation herein exhibits no toxicity to normal cells and exhibits pH-dependent antioxidant properties at neutral or physiological pH values, between approximately 6.5 to approximately 11.0 and is inactive as an antioxidant at acidic pH values between approximately 2.0 to approximately 6.4. Improved therapeutic agents and cytoprotecting devices are based on the newly discovered, pH dependent properties of polymer-coated nanoceria that provide selective cytoprotection.
摘要翻译：公开了方法，系统和组合物，其中正常的，未转化的，健康的生物细胞免受氧化应激，放射疗法和化学疗法，而患病的转化细胞，例如癌细胞，不提供生物相容的聚合物包被的纳米囊的保护本发明的组合物。本文所述的聚合物包被的纳米制品在正常细胞中没有毒性，并且在中性或生理学pH值（约6.5至约11.0之间）具有pH依赖性抗氧化剂性质，并且在约2.0至约6.4之间的酸性pH值下作为抗氧化剂无活性。改进的治疗剂和细胞保护装置基于提供选择性细胞保护的聚合物包被的纳米囊的新发现的pH依赖性质。

8. 发明授权

US08333993B1 Synthesis of polymer coated ceria nanoparticles for biomedical applications 有权
标题翻译：用于生物医学应用的聚合物包被的二氧化铈纳米颗粒的合成
公开(公告)号：US08333993B1
公开(公告)日：2012-12-18
申请号：US11965343
申请日：2007-12-27
申请人： Jesus Manuel Perez , Atul Asati , Sudip Nath
发明人： Jesus Manuel Perez , Atul Asati , Sudip Nath
IPC分类号： A61K9/14
CPC分类号： A61K9/5161 , A61K33/00
摘要： Procedures and methods for synthesizing biodegradable polymer coated nanoceria result in stable nanoparticle preparations in aqueous systems and physiological relevant colloidal solutions, such as phosphate buffer saline. The coated nanoceria preparations increase the nanoparticle concentration in aqueous or colloidal solutions as most needed for antioxidant, free-radical scavenger, and autocatalytic biomedical applications, including, biological, pharmacological and potential clinical use. To meet this need, a facile synthetic procedure for preparation of a biodegradable polymer-coated nanoceria is disclosed; the preferred biodegradable polymer is dextran. The synthesis method occurs under ambient conditions in an aqueous phase without the use of surfactants and results in a monodispersed preparation that is dextran-coated as determined by dynamic light scattering (DLS). Preliminary characterization of polymer coated nanoceria by XPS, TEM, XRD, and the like shows that these nanoparticles have the necessary physical properties for the desired biological potency, such as Ce+4/Ce+3 mixed valence state.
摘要翻译：用于合成可生物降解的聚合物包衣纳米片的方法和方法导致水性体系中的稳定的纳米颗粒制剂和生理相关的胶体溶液，例如磷酸盐缓冲盐水。包被的纳米制品增加了水溶胶或胶体溶液中的纳米颗粒浓度，这是抗氧化剂，自由基清除剂和自动催化生物医学应用中最需要的，包括生物学，药理学和潜在的临床应用。为了满足这种需要，公开了一种用于制备可生物降解的聚合物包被的纳米抗菌剂的简便的合成方法; 优选的可生物降解的聚合物是葡聚糖。合成方法在环境条件下在水相中发生，而不使用表面活性剂，并导致通过动态光散射（DLS）测定的葡聚糖涂覆的单分散制剂。通过XPS，TEM，XRD等对聚合物包被的纳米片的初步表征显示，这些纳米颗粒具有所需的生物效能的物理性能，例如Ce + 4 / Ce + 3混合价态。

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