Targeting apoptotic cells to enhance radiotherapy
靶向凋亡细胞以增强放射治疗
基本信息
- 批准号:10708827
- 负责人:
- 金额:$ 55.95万
- 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:2022-09-22 至 2027-08-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAdvanced Malignant NeoplasmApoptosisApoptoticBiochemicalBrachytherapyCASP3 geneCancer EtiologyCancer PatientCardiovascular DiseasesCellsCessation of lifeClinicalCombined Modality TherapyDepositionDevelopmentDiseaseDisease-Free SurvivalDistant MetastasisDoseDose LimitingDrug KineticsEarly treatmentElementsEpithelial CellsExternal Beam Radiation TherapyFailureFeedbackFluorescenceFollow-Up StudiesFunctional disorderGoalsHeterogeneityHydrolysisIatrogenesisImageImaging TechniquesImpaired cognitionIn VitroIntensity-Modulated RadiotherapyInvestigationLow Dose RadiationLymph Node DissectionsMagnetic Resonance ImagingMalignant NeoplasmsMalignant neoplasm of prostateMedical centerMental DepressionNanotechnologyOrganPatientsPelvic lymph node groupPenetrationPermeabilityPharmaceutical PreparationsPhase I Clinical TrialsPopulationPositron-Emission TomographyProdrugsPropertyProstateProstate Cancer therapyProstatic NeoplasmsQuality of lifeRadiationRadiation Dose UnitRadiation ToxicityRadiation therapyRadiation-Sensitizing AgentsRadical ProstatectomyRadioRadiosensitizationReactive Oxygen SpeciesRecurrenceRecurrent tumorReportingResearchResistance developmentSchemeSexual HealthSpecificityTechnologyTestingTherapeuticTimeTissuesToxic effectTreatment FailureTreatment ProtocolsTreatment outcomeUnited Statesaffective disturbanceandrogen deprivation therapycancer carecancer cellcancer radiation therapycancer therapychemotherapyclinical applicationdesigndiabetes riskdrug release profileempowermenthealth related quality of lifehigh riskimage guidedimage guided radiation therapyimaging facilitiesimaging probeimprovedin vivoin vivo evaluationirradiationmenmouse modelnanoassemblynanoparticlenanoparticle deliveryneoplastic cellnoveloptimal treatmentspartial responsepersonalized interventionprostate cancer cellprostate cancer modelradiation effectradiation responseself assemblyside effectsmall moleculesystemic toxicitytargeted treatmenttherapeutic evaluationtreatment effecttreatment responsetreatment strategytumortumor heterogeneitytumor xenograft
项目摘要
ABSTRACT
Radiation therapy is a potent element of standard cancer care, used in the treatment of over half of all
cancer patients. While the clinical benefits of radiotherapy are well documented, the dose to adjacent and
intermeshed normal organs and subsequent toxicity remains the biggest obstacle to continued escalation of
radiation doses to tumors in order to obtain cancer cures with RT. Significant number of patients will develop
locally persistent/recurrent tumors after radiotherapy. Therefore, radiosensitizing compounds, radiosensitizers,
have been developed to enhance tumor killing effects without escalation of radiation doses. However, their
clinical applications are limited due to invasive or insufficient tumor delivery and lack of specificity or systemic
toxicity. The goal of this project is to develop a prodrug-based therapeutic strategy empowered by a
nanotechnology pioneered by us —in cellulo nanoassembly—to amplify and enhance radiotherapeutic efficacy
for treating prostate cancer. Unlike common nanoparticle-based delivery approach, this delivery strategy does
not rely on the tumor enhanced permeability and retention effect. We propose to take advantage of the intrinsic
heterogeneous response to radiation therapy by targeting this initial population of apoptotic cells for depositing
radiosensitizers and enhancing radiotherapeutic effects. The project will develop and characterize the new
prodrug radiosensitizers for targeting apoptosis (Aim 1); investigate the pharmacokinetics, toxicity and validate
the in vivo treatment mechanism (Aim 2); and develop an image-guided treatment strategy, followed by a
comprehensive evaluation of the therapeutic benefit in orthotopic prostate cancer mouse models (Aim 3).
摘要
放射治疗是标准癌症护理的有力组成部分,用于治疗超过一半的癌症患者。
癌症患者。虽然放射治疗的临床益处是有据可查的,但邻近和
错综复杂的正常器官和随后的毒性仍然是继续升级的最大障碍
为了通过RT获得癌症治疗,对肿瘤的辐射剂量。相当数量的患者将发展为
放射治疗后局部持续性/复发性肿瘤。因此,辐射增敏化合物、辐射增敏剂、
已经开发出在不增加辐射剂量的情况下增强肿瘤杀灭效果的方法。然而,他们的
由于侵袭性或肿瘤传递不足,以及缺乏特异性或系统性,临床应用受到限制
毒性。该项目的目标是开发一种基于前药物的治疗策略,该策略由
由美国首创的纳米技术--在纤维纳米组装中--用于放大和增强放射治疗效果
治疗前列腺癌。与普通的纳米颗粒递送方法不同,这种递送策略
不依赖肿瘤的增透和滞留作用。我们建议利用固有的
靶向这一初始的凋亡细胞群沉积对放射治疗的异质性反应
放射增敏剂和增强放射治疗效果。该项目将开发和描述新的
靶向凋亡的前药放射增敏剂(AIM 1);药代动力学、毒性和有效性研究
体内治疗机制(目标2);并制定图像引导治疗策略,随后
对原位前列腺癌小鼠模型治疗效益的综合评价(目标3)。
项目成果
期刊论文数量(0)
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Jianghong Rao其他文献
Jianghong Rao的其他文献
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{{ truncateString('Jianghong Rao', 18)}}的其他基金
Targeting apoptotic cells to enhance radiotherapy
靶向凋亡细胞以增强放射治疗
- 批准号:
10538071 - 财政年份:2022
- 资助金额:
$ 55.95万 - 项目类别:
Copper-depleting nanotheranostics for treating triple negative breast cancer
用于治疗三阴性乳腺癌的铜消耗纳米治疗剂
- 批准号:
10004020 - 财政年份:2019
- 资助金额:
$ 55.95万 - 项目类别:
Copper-depleting nanotheranostics for treating triple negative breast cancer
用于治疗三阴性乳腺癌的铜消耗纳米治疗剂
- 批准号:
10231101 - 财政年份:2019
- 资助金额:
$ 55.95万 - 项目类别:
Copper-depleting nanotheranostics for treating triple negative breast cancer
用于治疗三阴性乳腺癌的铜消耗纳米治疗剂
- 批准号:
10900851 - 财政年份:2019
- 资助金额:
$ 55.95万 - 项目类别:
Copper-depleting nanotheranostics for treating triple negative breast cancer
用于治疗三阴性乳腺癌的铜消耗纳米治疗剂
- 批准号:
10413265 - 财政年份:2019
- 资助金额:
$ 55.95万 - 项目类别:
Copper-depleting nanotheranostics for treating triple negative breast cancer
用于治疗三阴性乳腺癌的铜消耗纳米治疗剂
- 批准号:
10684918 - 财政年份:2019
- 资助金额:
$ 55.95万 - 项目类别:
Copper-depleting nanotheranostics for treating triple negative breast cancer
用于治疗三阴性乳腺癌的铜消耗纳米治疗剂
- 批准号:
10472523 - 财政年份:2019
- 资助金额:
$ 55.95万 - 项目类别:
Beta-lactamase fluorescent probes for bacterial detection
用于细菌检测的 β-内酰胺酶荧光探针
- 批准号:
9309417 - 财政年份:2017
- 资助金额:
$ 55.95万 - 项目类别:
Nanoparticle-Based Triple Modality Imaging and Photothermal Therapy of Brain Tumors
基于纳米颗粒的脑肿瘤三模态成像和光热疗法
- 批准号:
10000853 - 财政年份:2016
- 资助金额:
$ 55.95万 - 项目类别: