Plasmonic nanoparticle-mediated immunotherapy to treat metastatic cancer
等离子纳米粒子介导的免疫疗法治疗转移性癌症
基本信息
- 批准号:10326341
- 负责人:
- 金额:$ 52.84万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-05-01 至 2025-01-31
- 项目状态:未结题
- 来源:
- 关键词:AblationAcuteAge-YearsAmericanAnimalsBiodistributionBiologicalBiophotonicsBladderBladder TissueCancer ModelCancer PatientCause of DeathCessation of lifeChronicClinicalClinical TrialsCombined Modality TherapyComplementary therapiesCystoscopyDisseminated Malignant NeoplasmDistantEffectivenessElectromagnetic EnergyElectromagnetic FieldsEstersFDA approvedFailureFluorescenceFormulationFractionationFutureGenerationsGeometryGoalsGoldHeat shock proteinsHumanImageImmune checkpoint inhibitorImmune responseImmunizeImmunocompetentImmunohistochemistryImmunophenotypingImmunotherapyImpairmentIndividualInductively Coupled Plasma Mass SpectrometryInjectionsIntravenousKDR geneLasersLengthLesionLeukocytesLifeLigand BindingLigandsLightMalignant NeoplasmsMalignant neoplasm of urinary bladderMapsMediatingMethodsModalityMorbidity - disease rateMusNanotechnologyNeoplasm MetastasisOperative Surgical ProceduresOpticsPD-1/PD-L1PatientsPenetrationPermeabilityPhotonsPhototherapyPositron-Emission TomographyProcessPropertyQuality of lifeRadical CystectomyRecurrenceRegimenReporterResearchResearch ProposalsSulfhydryl CompoundsSurfaceT-Cell ReceptorTechnologyTestingTherapeuticTimeToxic effectTransgenic OrganismsTreatment CostTreatment EfficacyTreatment ProtocolsTumor BurdenVaccinesWomanWorkabsorptionanti-PD-1anti-canceranti-tumor immune responsebasebioaccumulationbiomaterial compatibilitycancer cellcancer imagingcancer recurrencechemotherapyclinical translationcytokinedosimetryeffectiveness evaluationefficacy evaluationimmune activationimmune checkpointimmune checkpoint blockadeimmune resistanceimmunogenicimprovedin vivoindividualized medicineinnovationmenmortalitymouse modelmultimodalitynanoGoldnanoparticlenanoplasmonicnanotherapynew technologynext generationnovelnovel drug classnovel therapeuticsphantom modelphotothermal therapyplasmonicspreventprogrammed cell death ligand 1programmed cell death protein 1real time monitoringresistance mechanismresponsesynergismtherapeutically effectivetranslational goaltreatment optimizationtumortumor ablation
项目摘要
Bladder cancer (BC) is the 4th most common cancer in men and the 11th most common in women. BC
has the highest lifetime per-patient treatment cost of all cancers, mainly because of its high recurrence rate.
Also, regular invasive cystoscopy and the subsequent surgical treatment of recurrences impair patient quality
of life and cause significant morbidity. Therefore, there is a clear clinical need for novel technologies to
effectively treat BC, ultimately reducing tumor recurrences, treatment costs, number of radical cystectomies,
and mortality. A promising therapeutic platform for cancer is offered by gold nanoparticles (GNP). Taking
advantage of gold’s high biocompatibility, GNP can be injected intravenously and accumulate preferentially in
cancer cells due to the enhanced permeability and retention effect. Among GNP platforms, gold nanostars
(GNS) have great therapeutic potential due to the unique star-shaped geometry that dramatically enhances
light absorption and effective conversion into heat due to the plasmonic effect. This photothermal process can
be exploited to specifically ablate tumors and, importantly, to amplify the anti-tumor immune response following
the highly immunogenic thermal death of cancer cells. Relatedly, many cancers exploit immune checkpoints –
such as the interaction between programmed cell death 1 (PD-1) and its ligand (PD-L1) – to evade the anti-
cancer immune response. Recent immunotherapies disabling this immune resistance mechanism have shown
encouraging clinical results, are FDA approved in BC, but do not offer a permanent cure for most patients.
We thus propose to develop the GNS technology for use in SYnergistic iMmuno PHOtothermal
NanotherapY (SYMPHONY), a novel therapy that integrates nanotechnology, biophotonics, and
immunotherapy. The central hypothesis of this proposal is that combining GNS-mediated photothermal
nanotherapy with PD-1/PD-L1 immune checkpoint blockade will result in dramatic therapeutic synergism to
treat cancer metastasis. The rationale for this hypothesis is that photothermal therapy not only reduces tumor
burden by direct heat-based ablation, but also causes intense immune responses that can be amplified with
PD-1/PD-L1 immune checkpoint blockade. The specific aims are: (1) Fabricate and modulate optical properties
of next-generation plasmonics GNS to maximize photothermal therapy of deep tumors;; (2) Coat and
functionalize GNS to safely improve in vivo BC targeting;; and (3) Evaluate effectiveness of SYMPHONY
therapy for treating BC in murine models. The results of our research proposal intends to prove that
nanoparticle therapy and immunotherapy can be synergistically combined to produce an antitumor systemic
response far superior to either single therapy alone. We will also prove that SYMPHONY triggers an extremely
potent systemic response that cures both primary and distant lesions, producing a ‘vaccine’ effect to prevent
future BC recurrences. The proposed work will set the stage for SYMPHONY’s rapid future clinical translation
to improve life quality and reduce mortality of BC patients.
膀胱癌 (BC) 是男性中第 4 位最常见的癌症,女性中第 11 位最常见的癌症。 公元前
在所有癌症中,每位患者的生命周期治疗成本最高,主要是因为其复发率高。
此外,定期的侵入性膀胱镜检查和随后的复发手术治疗也会损害患者的质量
生命并导致显着的发病率。 因此,临床上显然需要新技术
有效治疗乳腺癌,最终减少肿瘤复发、治疗费用、根治性膀胱切除术的数量,
和死亡率。 金纳米粒子 (GNP) 提供了一个有前景的癌症治疗平台。 服用
利用金的高生物相容性,GNP可以静脉注射并优先在体内蓄积
由于增强的渗透性和滞留作用而对癌细胞产生影响。 在 GNP 平台中,金纳米星
(GNS) 具有巨大的治疗潜力,因为其独特的星形几何形状可显着增强
由于等离子体效应,光吸收并有效转化为热量。 这种光热过程可以
可用于专门消融肿瘤,并且重要的是,可增强随后的抗肿瘤免疫反应
癌细胞的高度免疫原性热死亡。 与此相关的是,许多癌症都会利用免疫检查点——
例如程序性细胞死亡 1 (PD-1) 与其配体 (PD-L1) 之间的相互作用 – 以逃避抗-
癌症免疫反应。 最近的免疫疗法已表明可以禁用这种免疫抵抗机制
令人鼓舞的临床结果,已在 BC 省获得 FDA 批准,但不能为大多数患者提供永久治愈。
因此,我们建议开发 GNS 技术用于协同免疫光热
NanotherapY(SYMPHONY)是一种集成了纳米技术、生物光子学和
免疫疗法。 该提案的中心假设是结合 GNS 介导的光热
纳米疗法与 PD-1/PD-L1 免疫检查点阻断将产生显着的治疗协同作用
治疗癌症转移。 该假设的基本原理是光热疗法不仅可以减少肿瘤
直接基于热的消融造成的负担,但也会引起强烈的免疫反应,这种反应可以通过以下方法放大:
PD-1/PD-L1 免疫检查点阻断。 具体目标是:(1) 制造和调制光学特性
下一代等离子体 GNS,以最大限度地提高深部肿瘤的光热疗法;;(2) 涂层和
使 GNS 功能化,以安全地改善体内 BC 靶向;;以及 (3) 评估 SYMPHONY 的有效性
在小鼠模型中治疗 BC 的疗法。 我们的研究计划的结果旨在证明
纳米颗粒疗法和免疫疗法可以协同组合以产生全身性抗肿瘤
反应远远优于单独的单一疗法。 我们还将证明 SYMPHONY 会引发极端的后果
有效的全身反应,可治愈原发性病变和远处病变,产生“疫苗”效应以预防
BC 未来的复发。 拟议的工作将为 SYMPHONY 未来快速临床转化奠定基础
提高 BC 患者的生活质量并降低死亡率。
项目成果
期刊论文数量(5)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Accurate in vivo tumor detection using plasmonic-enhanced shifted-excitation Raman difference spectroscopy (SERDS).
- DOI:10.7150/thno.53101
- 发表时间:2021
- 期刊:
- 影响因子:12.4
- 作者:Strobbia P;Cupil-Garcia V;Crawford BM;Fales AM;Pfefer TJ;Liu Y;Maiwald M;Sumpf B;Vo-Dinh T
- 通讯作者:Vo-Dinh T
Intravital optical imaging for immune cell tracking after photoimmunotherapy with plasmonic gold nanostars.
- DOI:10.1088/1361-6528/ac893a
- 发表时间:2022-08-31
- 期刊:
- 影响因子:3.5
- 作者:
- 通讯作者:
Nanoplasmonics Enabling Cancer Diagnostics and Therapy.
- DOI:10.3390/cancers14235737
- 发表时间:2022-11-22
- 期刊:
- 影响因子:5.2
- 作者:
- 通讯作者:
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Tuan Vo-Dinh其他文献
Tuan Vo-Dinh的其他文献
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{{ truncateString('Tuan Vo-Dinh', 18)}}的其他基金
Integrated Acoustofluidic Plasmonic Molecular Diagnostic System for Detecting MicroRNA Biomarkers
用于检测 MicroRNA 生物标志物的集成声流控等离子体分子诊断系统
- 批准号:
10580345 - 财政年份:2020
- 资助金额:
$ 52.84万 - 项目类别:
Integrated Acoustofluidic Plasmonic Molecular Diagnostic System for Detecting MicroRNA Biomarkers
用于检测 MicroRNA 生物标志物的集成声流控等离子体分子诊断系统
- 批准号:
10542811 - 财政年份:2020
- 资助金额:
$ 52.84万 - 项目类别:
Integrated Acoustofluidic Plasmonic Molecular Diagnostic System for Detecting MicroRNA Biomarkers
用于检测 MicroRNA 生物标志物的集成声流控等离子体分子诊断系统
- 批准号:
10322659 - 财政年份:2020
- 资助金额:
$ 52.84万 - 项目类别:
Nanoplasmonics-based molecular analysis tool for molecular biomarkers of cancer
基于纳米等离子体的癌症分子生物标志物分子分析工具
- 批准号:
9321908 - 财政年份:2015
- 资助金额:
$ 52.84万 - 项目类别:
Nanoplasmonics-based molecular analysis tool for molecular biomarkers of cancer
基于纳米等离子体的癌症分子生物标志物分子分析工具
- 批准号:
9140063 - 财政年份:2015
- 资助金额:
$ 52.84万 - 项目类别:
Nonobiosensors for Probing Chemical Exposure and Metabolism Pathways of Individua
用于探测个体化学暴露和代谢途径的非生物传感器
- 批准号:
7628387 - 财政年份:2007
- 资助金额:
$ 52.84万 - 项目类别:
Nonobiosensors for Probing Chemical Exposure and Metabolism Pathways of Individua
用于探测个体化学暴露和代谢途径的非生物传感器
- 批准号:
7470578 - 财政年份:2007
- 资助金额:
$ 52.84万 - 项目类别:
Nonobiosensors for Probing Chemical Exposure and Metabolism Pathways of Individua
用于探测个体化学暴露和代谢途径的非生物传感器
- 批准号:
7279531 - 财政年份:2007
- 资助金额:
$ 52.84万 - 项目类别:
Ultra-High-Throughput Screening Based on Surface Enhance
基于表面增强的超高通量筛选
- 批准号:
7240228 - 财政年份:2006
- 资助金额:
$ 52.84万 - 项目类别:
Ultra-High-Throughput Screening (uHTS) Based on Surface*
基于表面的超高通量筛选 (uHTS)*
- 批准号:
7318325 - 财政年份:2006
- 资助金额:
$ 52.84万 - 项目类别:
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