siRNA-based Gold Nanoparticles as a Therapeutic Enhancer for Triple Negative Breast Cancer (TNBC) Radiotherapy
基于 siRNA 的金纳米颗粒作为三阴性乳腺癌 (TNBC) 放射治疗的治疗增强剂
基本信息
- 批准号:10729127
- 负责人:
- 金额:$ 7.62万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-07-10 至 2025-06-30
- 项目状态:未结题
- 来源:
- 关键词:AdjuvantAnimalsBreast Cancer CellBreast Cancer ModelBreast Cancer therapyCell SurvivalCellsChemicalsClinicalCombination Drug TherapyCombination immunotherapyDNA DamageDataDrug CarriersDrug Delivery SystemsDyesEnhancersEnvironmentEnzyme-Linked Immunosorbent AssayExhibitsFutureGoalsGrowthImmuneImmune systemImmunologic StimulationImmunosuppressionImmunotherapeutic agentImmunotherapyIn VitroIncubatedInterventionMalignant NeoplasmsMeasuresMicroscopyMolecularMouse Cell LineMusNatureNeoadjuvant TherapyNeoplasm MetastasisOpticsOutcomePathway interactionsPatientsPatternPhenotypePrimary NeoplasmProductionPrognosisPropertyPublic HealthPublishingQuantitative Reverse Transcriptase PCRRNA chemical synthesisRNA deliveryRadiationRadiation therapyRadiation-Sensitizing AgentsRadiosensitizationResearchRoleSmall Interfering RNASurvival RateTestingTherapeuticTherapeutic EffectTherapeutic immunosuppressionTransforming Growth Factor betaTransmission Electron MicroscopyTreatment EfficacyTumor ImmunityTumor TissueTumor-infiltrating immune cellsWorkXenograft Modelanti-canceranti-tumor immune responseantitumor effectcancer cellcancer immunotherapycancer radiation therapycancer typecyanine dye 5cytokinedesignimmune checkpoint blockersimmunogenic cell deathimmunogenicityimmunomodulatory therapiesimmunoregulationimprovedin vivoin vivo optical imaginginnovationinterestmalignant breast neoplasmmouse modelmultimodalitynanoGoldnovel strategiesprospectiveradiation effectrecruitresponsetreatment responsetriple-negative invasive breast carcinomatumortumor growthtumor microenvironmentuptakezeta potential
项目摘要
ABSTRACT
Radiation therapy (RT) modulates immunological properties of tumor microenvironment (TME) to stimulate
antitumor immune response. However, RT initiates immunosuppressive mechanisms as well and therefore
diminishing the effects of RT immuno-stimulation. One of the main RT immunosuppressive modes is exerted by
an increase in TGF production that in breast cancers (BC) has an additive effect on already high TGF levels
produced by cancer cells themselves. Triple negative breast cancer (TNBC) in particular, was demonstrated to
have higher TGF levels compared to other BCs, and this finding correlated with increased tumor grade and
invasiveness, and a diminished patient survival. Consequently, RT induced increase in TGF within the TME
may further potentiate invasiveness and metastatic potential of TNBC. Due to stimulatory aspects of RT
immunomodulation, RT has gained interest as a prospective therapeutic enhancer in cancer immunotherapy,
such as immune checkpoint blockers, that has shown great potential in improving local control and overall
survival in select cancers. Unfortunately, in most forms of BC, including TNBC, response to immunotherapy
remains modest. Our long-term goal is to use RT to enhance TNBC response to immunotherapy by taking
advantage of RT immunomodulatory potential. Antitumor RT effects, including TME immunomodulation can be
improved by using radiosensitizers, such as gold nanoparticles (AuNP). Furthermore, AuNPs can also serve as
a drug delivery system by conjugation of small interfering RNAs (siRNAs). In this project we propose to use
AuNPs functionally modified by TGF siRNA to simultaneously enhance RT immunomodulation and counteract
the immunosuppressive effects related to the increased TGF production. This approach will enhance RT
antitumor effects and create a favorable TME environment for better response to future immunotherapies. This
will be tested by the following specific aims: Aim 1: To synthesize and characterize AuNP-siRNATGF1; Aim
2: To investigate the therapeutic effect of combination of RT and AuNP-siRNATGFβ1 in in vitro and in vivo
mouse TNBC model. The proposed studies in determining the potential of AuNPs simultaneously target
antitumor and immunomodulatory RT effects will provide critical information for improving TNBC response to
immune checkpoint blockers and for designing future RT/ immune checkpoint blockers multimodal TNBC
therapies.
摘要
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Branislava Janic其他文献
Branislava Janic的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
相似海外基金
The earliest exploration of land by animals: from trace fossils to numerical analyses
动物对陆地的最早探索:从痕迹化石到数值分析
- 批准号:
EP/Z000920/1 - 财政年份:2025
- 资助金额:
$ 7.62万 - 项目类别:
Fellowship
Animals and geopolitics in South Asian borderlands
南亚边境地区的动物和地缘政治
- 批准号:
FT230100276 - 财政年份:2024
- 资助金额:
$ 7.62万 - 项目类别:
ARC Future Fellowships
The function of the RNA methylome in animals
RNA甲基化组在动物中的功能
- 批准号:
MR/X024261/1 - 财政年份:2024
- 资助金额:
$ 7.62万 - 项目类别:
Fellowship
Ecological and phylogenomic insights into infectious diseases in animals
对动物传染病的生态学和系统发育学见解
- 批准号:
DE240100388 - 财政年份:2024
- 资助金额:
$ 7.62万 - 项目类别:
Discovery Early Career Researcher Award
RUI:OSIB:The effects of high disease risk on uninfected animals
RUI:OSIB:高疾病风险对未感染动物的影响
- 批准号:
2232190 - 财政年份:2023
- 资助金额:
$ 7.62万 - 项目类别:
Continuing Grant
RUI: Unilateral Lasing in Underwater Animals
RUI:水下动物的单侧激光攻击
- 批准号:
2337595 - 财政年份:2023
- 资助金额:
$ 7.62万 - 项目类别:
Continuing Grant
A method for identifying taxonomy of plants and animals in metagenomic samples
一种识别宏基因组样本中植物和动物分类的方法
- 批准号:
23K17514 - 财政年份:2023
- 资助金额:
$ 7.62万 - 项目类别:
Grant-in-Aid for Challenging Research (Exploratory)
Analysis of thermoregulatory mechanisms by the CNS using model animals of female-dominant infectious hypothermia
使用雌性传染性低体温模型动物分析中枢神经系统的体温调节机制
- 批准号:
23KK0126 - 财政年份:2023
- 资助金额:
$ 7.62万 - 项目类别:
Fund for the Promotion of Joint International Research (International Collaborative Research)
Using novel modelling approaches to investigate the evolution of symmetry in early animals.
使用新颖的建模方法来研究早期动物的对称性进化。
- 批准号:
2842926 - 财政年份:2023
- 资助金额:
$ 7.62万 - 项目类别:
Studentship
Study of human late fetal lung tissue and 3D in vitro organoids to replace and reduce animals in lung developmental research
研究人类晚期胎儿肺组织和 3D 体外类器官在肺发育研究中替代和减少动物
- 批准号:
NC/X001644/1 - 财政年份:2023
- 资助金额:
$ 7.62万 - 项目类别:
Training Grant














{{item.name}}会员




