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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. 发明申请

US20210228733A1 METHODS AND COMPOSITIONS FOR THERANOSTIC NANOPARTICLES 有权
公开(公告)号：US20210228733A1
公开(公告)日：2021-07-29
申请号：US17228286
申请日：2021-04-12
申请人： Annette Khaled , Jesus Manuel Perez Figueroa , Santimukul Santra , Charalambos Kaittanis , Oscar Santiesteban , Jan Grimm , Hampton Sessions
发明人： Annette Khaled , Jesus Manuel Perez Figueroa , Santimukul Santra , Charalambos Kaittanis , Oscar Santiesteban , Jan Grimm , Hampton Sessions
IPC分类号： A61K47/68 , A61K45/06 , A61K51/10 , A61K51/12 , A61K38/08 , A61K38/10 , A61K47/69
摘要： Disclosed are compositions and methods for identifying a solid tumor cell target. Compositions and methods for treating prostate cancer are also disclosed. Further, cancer therapeutic compositions comprising CT20p are disclosed. Nanoparticles that are conjugated with a targeting ligand that is a substrate for a solid tumor-specific cell protein are disclosed.

8. 发明授权

US08372944B1 Synthesis of hyperbranched amphiphilic polyester and theranostic nanoparticles thereof 有权
公开(公告)号：US08372944B1
公开(公告)日：2013-02-12
申请号：US12417017
申请日：2009-04-02
申请人： J. Manuel Perez , Santimukul Santra
发明人： J. Manuel Perez , Santimukul Santra
IPC分类号： C08G63/00 , C07C61/00 , C07C27/10
CPC分类号： A61K9/5138 , A61K9/146 , A61K9/1647 , A61K9/5153 , A61K9/5192 , A61K31/337 , A61K31/505 , A61K31/519 , A61K31/7072 , A61K47/48907 , A61K47/6935 , A61K49/0032 , A61K49/0093 , C08G63/06 , C08G63/664 , C08G63/6852 , C08G63/87 , C08G63/90 , C08G63/912 , C08G83/005 , C08G83/006
摘要： A method of making a hyperbranched amphiphilic polyester compound includes drying under vacuum a mixture of 2-(4-hydroxybutyl)-malonic acid and p-toluene sulphonic acid as catalyst. The vacuum is then released with a dry inert gas after drying. The dried mixture is heated under the inert gas at a temperature sufficient for polymerization. The inert gas is evacuated while continuing to heat the mixture. The formed polymer is then dissolved in dimethylformamide and precipitated out by adding methanol. Modifications of the method yield nanoparticles of polyesters having properties suited for coencapsulating fluorescent dyes together with therapeutic drugs, resulting in theranostic nanoparticles, that is, nanoparticles useful in both therapeutic treatments and diagnostic methods.

9. 发明授权

US08236284B1 Multimodal, multifunctional polymer coated nanoparticles 失效
标题翻译：多模多功能聚合物涂层纳米粒子
公开(公告)号：US08236284B1
公开(公告)日：2012-08-07
申请号：US12416993
申请日：2009-04-02
申请人： J. Manuel Perez , Santimukul Santra
发明人： J. Manuel Perez , Santimukul Santra
IPC分类号： A61K9/14 , A01N59/16
CPC分类号： A61K49/0093 , A61K47/551 , A61K47/6923 , B82Y5/00 , Y10S977/773 , Y10S977/777
摘要： Disclosed are nanoparticles having a metallic core consisting essentially of superparamagnetic iron oxide; a polymeric coat surrounding said core, the coat having a matrix of polyacrylic acid and forming an outer periphery of said nanoparticle; a plurality of hydrophobic pockets formed by the polymeric coat; a plurality of carboxylic groups along an outer periphery of the polymeric coat and effective to conjugate with a predetermined targeting ligand which functionalizes the nanoparticle; a lipophylic fluorescent dye encapsulated in the plurality of hydrophobic pockets; and a drug encapsulated in the plurality of hydrophobic pockets. Associated methods of making the nanoparticles and of treatments using the nanoparticles are also disclosed.
摘要翻译：公开了具有基本上由超顺磁性氧化铁组成的金属芯的纳米颗粒; 围绕所述芯的聚合物涂层，所述涂层具有聚丙烯酸基质并形成所述纳米颗粒的外周; 由聚合物涂层形成的多个疏水口袋; 多个沿着聚合物涂层的外周的羧基，并有效地与功能化纳米颗粒的预定的靶向配体结合; 密封在所述多个疏水口袋中的脂质荧光染料; 和封装在多个疏水口袋中的药物。还公开了制备纳米颗粒和使用纳米颗粒的处理的相关方法。

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