A nanoparticle platform for targeted delivery of therapeutic agents to retinal pigment epithelial or choroidal endothelial cells

用于将治疗剂靶向递送至视网膜色素上皮或脉络膜内皮细胞的纳米颗粒平台

• 批准号: 9195104
• 负责人: Glenn Yiu
• 金额: $ 20.66万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9195104
• 关键词: Affect; Affinity; Age related macular degeneration; Angiogenesis Inhibitors; Animals; Anterior; Applications Grants; Area; Binding; Blindness; Cell Culture Techniques; Cells; Cholic Acids; Choroidal Neovascularization; Clinical; Clinical Research; Cultured Cells; Defect; Development; Diagnostic; Doxorubicin; Drug Delivery Systems; Drug Targeting; Drug usage; Elderly; Electron Transport; Encapsulated; Endocytosis; Endophthalmitis; Endothelial Cells; Epithelial; Exudative age-related macular degeneration; Eye; Faculty; Fluorescence; Fluorescent Dyes; Fluorescent Probes; Functional disorder; Goals; Human; Image; Imaging technology; Inflammatory; Injectable; Injection of therapeutic agent; Integrins; Intravenous; Intravenous Drug Delivery Systems; Laboratories; Lasers; Libraries; Ligand Binding; Ligands; Light; Mentors; Metabolic; Monitor; Mus; Neurons; Ophthalmoscopy; Optical Coherence Tomography; PUVA Photochemotherapy; Pathogenesis; Peptide Library; Peptides; Permeability; Pharmaceutical Preparations; Pharmacology; Photosensitization; Play; Porphyrins; Protocols documentation; Regulation; Research; Retinal; Retinal Detachment; Retinal Diseases; Retinal Pigments; Risk; Role; Scanning; Scientist; Singlet Oxygen; Source; Specialist; Specificity; Structure; Structure of retinal pigment epithelium; Surface; System; Tail; Techniques; Technology; Testing; Therapeutic; Therapeutic Agents; Tissues; Toxic effect; Training; Transducers; Translational Research; Veins; Verteporfin; Viral; Wild Type Mouse; adaptive optics; base; biomaterial compatibility; cancer clinical trial; cancer therapy; cell type; combinatorial; cost; crosslink; fetal; gene therapy; in vivo; interest; intravitreal injection; mouse model; nanoparticle; nanotherapeutic; overexpression; particle; public health relevance; screening; skills; small molecule; subretinal injection; targeted delivery; targeted treatment; tool

 DESCRIPTION (provided by applicant): The retinal pigment epithelium (RPE) and choroidal vasculature play important roles in the pathophysiology of age-related macular degeneration (AMD), a leading cause of blindness in the elderly. Current therapeutic strategies rely on intravitreal or subretinal injections to deliver the pharmacologic agents. However, these injections are invasive and costly, and may adversely affect other ocular structures. The goal of this study is to develop a drug delivery system that could be given intravenously, and directly targeted to RPE or choroidal vessels for the treatment of retinal diseases like AMD. Our hypothesis is that nanoporphyrins, a multifunctional porphyrin/cholic acid-based micellar nanoparticle, that can 1) efficiently encapsulate fluorescent dyes or pharmacologic compounds, 2) release the payload when triggered with an external light source, and 3) be decorated with tissue-specific ligands, can be used to provide both diagnostic and therapeutic functions in the eye. Using confocal scanning laser ophthalmoscopy (SLO) technology, nanoporphyrins can be visualized and triggered to release a drug directly to RPE or CECs. The specific aims of this study are to 1) to discover RPE and CEC-specific peptide ligands using combinatorial library screening, 2) to visualize and trigger nanoporphyrins in mouse eyes using SLO imaging, and 3) to test transducers that efficiently convert light to heat for photothermal therapy (PTT) and to singlet oxygen for PDT, similAs an academic clinician-scientist and vitreoretinal specialist, I have both clinical and research interests in As an academic clinician-scientist and vitreoretinal specialist, I have both clinical and research interests in understanding the mechanisms of retinal diseases. With a strong background in neuronal cell culture and clinical ophthalmic imaging, I am well-prepared to pursue translational research to study the pathogenesis and treatment of AMD. UC Davis offers a world-class faculty and facilities that has the potential to facilitate my training in areas of nanotherapeutics, drug delivery, and live animal ocular imaging. The mentoring and skills acquired with this grant proposal will enable me to attain expertise in translational AMD research.

 描述（由适用提供）：视网膜色素上皮（RPE）和脉络膜脉管系统在与年龄相关的黄斑变性（AMD）的病理生理学中起重要作用，这是最古老的失明的主要原因。当前的治疗策略依靠玻璃体内或视网膜下注射来提供药物。但是，这些注射是侵入性且昂贵的，可能会对其他眼睛结构产生不利影响。这项研究的目的是开发一种可以静脉注射的药物输送系统，并直接针对RPE或脉络膜血管来治疗AMD等残留疾病。我们的假设是，一种多功能卟啉/胆酸基于多功能的胶束胶束纳米粒子，可以有效地封装荧光染料或药物化合物，2）释放有效载荷时，当用外部光源触发时，以及3）可以使用象征性的毛孔来诊断，并可以诊断出诊断。使用共聚焦扫描激光眼镜检查（SLO）技术，可以将纳米磷脂可视化并触发，以直接释放出RPE或CEC的药物。 The specific aims of this study are to 1) to discover RPE and CEC-specific pepper ligands using combinatorial library screening, 2) to visualize and trigger nanoporphyrins in mouse eyes using SLO imaging, and 3) to test transducers that effectively convert light to heat for photothermal therapy (PTT) and to single oxygen for PDT, similarAs an academic clinical-scientist and vitreoletinal专家是我作为学术临床科学家和玻璃体遗传学专家的临床和研究兴趣，我在理解残留疾病的机制方面具有临床和研究兴趣。在神经元细胞培养和临床眼科成像方面具有强大的背景，我已经准备好进行翻译研究以研究AMD的发病机理和治疗。加州大学戴维斯分校提供了世界一流的教职员工和设施，有可能促进我在纳米疗法，药物输送和活动物眼影像学领域进行培训。通过这项赠款提案获得的心理和技能将使我能够在翻译AMD研究中获得专业知识。