Novel nanoparticles to stimulate therapeutic angiogenesis in peripheral arterial disease
刺激外周动脉疾病治疗性血管生成的新型纳米颗粒
基本信息
- 批准号:10616740
- 负责人:
- 金额:$ 53.03万
- 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:2022-05-02 至 2026-04-30
- 项目状态:未结题
- 来源:
- 关键词:AcuteAffectAftercareAlternative TherapiesAnilineAnimal ModelApoptosisArteriesBindingBiocompatible MaterialsBiodistributionBlood GlucoseBlood VesselsBlood coagulationBlood flowCD34 geneCell SurvivalCellsCholesterolChronicCollateral CirculationComplementary DNACytoprotectionDataDetectionDevelopmentDiarrheaDiseaseElastomersElderlyErythropoietin ReceptorEvaluationGoalsGrowth FactorHeadacheHematopoietic Stem Cell MobilizationHemorrhageHypertensionHypoxiaImpairmentIn SituIn VitroIndividualInduction of ApoptosisInflammationInterventionIntramuscularIschemiaLegLigationLocationLower ExtremityMediatingModalityMonitorMorbidity - disease rateMultimodal ImagingNamesNanotechnologyObstructionOperative Surgical ProceduresPain in lower limbPatientsPeripheralPeripheral arterial diseasePersonsPharmaceutical PreparationsPharmacotherapyPolymersPredispositionPropertyQuality of lifeReagentResearchResearch Project GrantsResearch SupportRoleSiteStressStructureTherapeuticTherapeutic AgentsTherapeutic EffectTherapeutic InterventionTissue EngineeringTissuesTreatment EfficacyUnited StatesVascular DiseasesWorkangiogenesisanimal model selectionantibody conjugateartery occlusionbiomaterial compatibilityblood perfusionblood vessel developmentcombatcommon treatmenteffective therapyeffectiveness evaluationelastomericendothelial stem cellfabricationfemoral arteryfluorescence imaginggene therapyimaging modalityimaging propertiesimprovedin vivoin vivo evaluationinnovationlimb ischemialimb lossmortalitymouse modelnanoparticlenon-invasive imagingnovelnovel therapeuticsphotoacoustic imagingpreventrecruitreduce symptomsrevascularization surgeryside effectstem cellssuccesstherapeutic angiogenesistherapeutic effectivenesstherapeutically effectivetool
项目摘要
ABSTRACT
Peripheral arterial disease (PAD) is a severe impairment of arterial vessels resulting in obstruction of normal
blood flow in the legs, leading to acute or chronic lower limb ischemia and subsequently high morbidity and
mortality rates. Common treatments for PAD, such as medications and surgical revascularization, have several
limitations. For instance, medications used to lower cholesterol, reduce high blood pressure, control blood sugar,
prevent blood clots, and relieve symptoms like leg pains may delay onset. Still, they cannot treat the established
disease directly and often cause side effects, including bleeding, headache, and diarrhea. Meanwhile, many
elderly PAD patients cannot undergo surgical options. Therefore, it is vital to develop an alternative therapy to
treat PAD. Our long-term goal is to develop novel degradable dual-modal imaging nanoparticles (DINPs) to
precisely deliver therapeutic reagents that provide cell protection and facilitate the formation of blood vessels de
novo at ischemic sites while allowing detection of the NP location and monitoring of their therapeutic
effectiveness for PAD treatment. We have three specific aims: (1) To synthesize, characterize and optimize our
biodegradable dual-modal fluorescent/photoacoustic elastomers named biodegradable photoluminescent
polymers-aniline tetramers (BPLPAT), (2) To formulate and analyze DINPs made of optimized BPLPATs and
loaded with therapeutic reagents for facilitating cell protection and angiogenesis, and (3) To evaluate the
effectiveness of DINPs to treat PAD in vivo using animal models. Innovative aspects of this research are i) the
use of our novel BPLPAT material allowing both fluorescent and deep-tissue photoacoustic imaging opportunities
to detect the in vivo distribution of these NPs and evaluate their degradation assessment; ii) development of
DINPs based on recent advances in nanotechnology and tissue engineering providing a unique strategy to
deliver new therapeutic agents to the ischemic site in order to enhance cellular protection and promote
angiogenesis in situ under hypoxic conditions such as ischemic tissues. The rigor of prior research and
scientific feasibility of our developed DINPs are well-established as we have already demonstrated (1) their
detectability via both fluorescence and photoacoustic imaging, (2) the retention of DINPs loaded with therapeutic
agents at the ischemic zones, (3) the release of therapeutic compounds in a sustained manner, and (4) their
capacity to provide cell protection and promote angiogenesis to recover blood perfusion after ischemia. The
success of our research will provide a novel therapy for the effective treatment of PAD.
摘要
外周动脉疾病(PAD)是一种严重的动脉血管损伤,导致正常血管阻塞,
腿部血流,导致急性或慢性下肢缺血,随后发病率高,
死亡率。PAD的常见治疗方法,如药物治疗和手术血运重建,有几个
局限性。例如,用于降低胆固醇,降低高血压,控制血糖,
防止血栓形成,缓解腿部疼痛等症状,可能会延迟发病。然而,他们不能把既定的
疾病直接,并经常引起副作用,包括出血,头痛和腹泻。与此同时,许多
老年PAD患者不能接受手术治疗。因此,开发一种替代疗法至关重要,
治疗PAD。我们的长期目标是开发新型可降解双模成像纳米颗粒(DINPs),
精确地递送提供细胞保护和促进血管形成的治疗试剂,
同时允许检测NP的位置并监测其治疗效果。
有效治疗PAD。我们有三个具体目标:(1)合成,表征和优化我们的
一种可生物降解的双模态荧光/光声弹性体
聚合物-苯胺四聚体(BPLPAT),(2)配制和分析由优化的BPLPAT和
装载有用于促进细胞保护和血管生成的治疗试剂,以及(3)为了评估
使用动物模型在体内治疗PAD的DINPs的有效性。本研究的创新之处在于:i)
使用我们的新型BPLPAT材料,允许荧光和深层组织光声成像机会
检测这些NP的体内分布并评价其降解评估; ii)开发
DINPs基于纳米技术和组织工程的最新进展,提供了独特的策略,
将新的治疗剂递送到缺血部位以增强细胞保护和促进
在缺氧条件下原位血管生成,例如缺血组织。先前研究的严谨性和
我们开发的DINPs的科学可行性已经确立,因为我们已经证明了(1)
通过荧光和光声成像的可检测性,(2)装载治疗药物的DINPs的保留
药物在缺血区的作用,(3)治疗化合物以持续的方式释放,和(4)它们的
提供细胞保护和促进血管生成以恢复缺血后的血液灌注的能力。的
本研究的成功将为PAD的有效治疗提供一种新的治疗方法。
项目成果
期刊论文数量(0)
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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RALPH P. MASON其他文献
RALPH P. MASON的其他文献
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{{ truncateString('RALPH P. MASON', 18)}}的其他基金
Novel nanoparticles to stimulate therapeutic angiogenesis in peripheral arterial disease
刺激外周动脉疾病治疗性血管生成的新型纳米颗粒
- 批准号:
10462909 - 财政年份:2022
- 资助金额:
$ 53.03万 - 项目类别:
Novel nanoparticles to stimulate therapeutic angiogenesis in peripheral arterial disease
刺激外周动脉疾病治疗性血管生成的新型纳米颗粒
- 批准号:
10756875 - 财政年份:2022
- 资助金额:
$ 53.03万 - 项目类别:
Vascular image-guided optimization of response (VIGOR) to therapy in kidney cancer
血管图像引导肾癌治疗反应优化 (VIGOR)
- 批准号:
10646312 - 财政年份:2020
- 资助金额:
$ 53.03万 - 项目类别:
Vascular image-guided optimization of response (VIGOR) to therapy in kidney cancer
血管图像引导肾癌治疗反应优化 (VIGOR)
- 批准号:
10442463 - 财政年份:2020
- 资助金额:
$ 53.03万 - 项目类别:
Vascular image-guided optimization of response (VIGOR) to therapy in kidney cancer
血管图像引导肾癌治疗反应优化 (VIGOR)
- 批准号:
10058644 - 财政年份:2020
- 资助金额:
$ 53.03万 - 项目类别:
Vascular image-guided optimization of response (VIGOR) to therapy in kidney cancer
血管图像引导肾癌治疗反应优化 (VIGOR)
- 批准号:
10171568 - 财政年份:2020
- 资助金额:
$ 53.03万 - 项目类别:
PROGNOSTIC RADIOLOGY AND THE PATHOPHYSIOLOGY OF TUMORS
预后放射学和肿瘤病理生理学
- 批准号:
8363897 - 财政年份:2011
- 资助金额:
$ 53.03万 - 项目类别:
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