Theranostic Nanovesicles for Ocular Angiogenesis Therapy
用于眼部血管生成治疗的治疗诊断纳米囊泡
基本信息
- 批准号:10556380
- 负责人:
- 金额:$ 24.56万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-02-01 至 2024-01-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAdvanced DevelopmentAdverse effectsAge related macular degenerationAngiogenesis InhibitorsAnimal ModelBindingBiologicalBlindnessCataractCellsChoroidal NeovascularizationDeteriorationDeveloped CountriesDiabetic RetinopathyDiseaseDrug Delivery SystemsDrug FormulationsDrug KineticsElectroporationEndophthalmitisEngineeringExudative age-related macular degenerationEyeEye diseasesFormulationImageIn VitroInjectionsIntegrin alpha5beta1Integrin alphaVbeta3IntegrinsIonizing radiationLabelLasersLegal BlindnessLesionLiquid substanceMagnetismMalignant NeoplasmsMediatingMedicalMesenchymal Stem CellsMethodsModalityModificationMusOphthalmologyPUVA PhotochemotherapyPathologic NeovascularizationPatientsPenetrationPeptidesPersonsPharmaceutical PreparationsPosterior eyeball segment structurePropertyRattusRecoveryResearchResolutionRetinaRetinal DetachmentRetinal DiseasesStem Cell DevelopmentSystemTestingTherapeutic AgentsTimeTissuesTreatment EfficacyVascular DiseasesVascular Endothelial Growth FactorsVisionVisualizationagedalternative treatmentangiogenesisantagonistbiomaterial compatibilitycombatcytotoxicitydrug distributionexosomeimaging modalityimmunogenicityimmunoregulationimprovedin vivoinhibitorintravitreal injectioniron oxideiron oxide nanoparticlelaminin gamma 1laser photocoagulationlegally blindmolecular imagingnanocarriernanoengineeringnanoparticlenanoparticle deliverynanotechnology platformnanovesicleneovascularneovasculaturenon-invasive imagingnovelnovel therapeuticsocular angiogenesisocular neovascularizationparticlequantitative imagingselective expressionserial imagingstandard of carestem cell exosomesstem cellssuperparamagnetismtheranosticstherapeutic angiogenesistomographytooltumor growth
项目摘要
The current standard of care for wet age-related macular degeneration (AMD) with intravitreal injections of
vascular endothelial growth factor (VEGF) inhibitors has transformed the treatment paradigm. However, many
AMD patients with choroidal neovascularization (CNV) either fail to respond to anti-VEGF therapy or suffer
from complications associated with repeated intravitreal injections. Therefore, there is great need for
developing alternative treatment modalities, including novel therapeutic agents and delivery methods, to
combat CNV for patients with AMD.
The selective expression of certain integrins on choroidal and retinal neovasculature makes integrin an
ideal target, while delivery of integrin antagonists can be engineered using stem cell-derived nanovesicle
system that is biocompatible and amenable for crossing the ocular barriers. We hypothesize that modification
of the stem cell-derived, superparamagnetic iron oxide particle (SPIO)-labeled exosomes to deliver an integrin
antagonist will provide a potent theranostic agent to effectively inhibit or regress CNV with the ability to directly
visualize and quantitatively assess drug distribution in vivo. In Specific Aim 1, we will develop and fully
characterize the nanovesicle formulations and test their cytotoxicity, antiangiogenic property, as well as
magnetic particle imaging (MPI) sensitivity. In Specific Aim 2, we will test the hypothesis that the engineered
nanovesicle system improves the therapeutic efficacy of CNV in vivo and enables MPI imaging for longitudinal
quantification of drug distribution. In this aim, we will determine the effect of SPIO-labeled, drug-conjugated
nanovesicles on Iaser-induced CNV and analyze the kinetics of drug distribution by noninvasive MPI imaging.
The proposed study brings a unique combination of expertise in ophthalmology, drug delivery, MPI
imaging, and animal model of retinal diseases, to address the critical challenges for efficient drug delivery into
the posterior segment of the eye. Successful completion of the proposed activities will have vast ramifications
for advancing the development of stem cell-derived nanovesicles as novel theranostic agent for treating ocular
vascular diseases and other angiogenesis-related disorders.
目前治疗湿性年龄相关性黄斑变性(AMD)的标准是玻璃体内注射
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('Yingli Fu', 18)}}的其他基金
Theranostic Nanovesicles for Ocular Angiogenesis Therapy
用于眼部血管生成治疗的治疗诊断纳米囊泡
- 批准号:
10351754 - 财政年份:2022
- 资助金额:
$ 24.56万 - 项目类别:
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