Photodynamic Priming for Bidirectional Modulation of Drug Transport Across the Blood-Brain Tumor Barrier

光动力引发双向调节药物跨血脑肿瘤屏障转运

基本信息

  • 批准号:
    10057075
  • 负责人:
  • 金额:
    $ 20.35万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2020
  • 资助国家:
    美国
  • 起止时间:
    2020-07-01 至 2023-03-31
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY Most primary brain tumors are managed by maximal safe resection followed by chemotherapy and radiation to treat residual and potentially infiltrative tumor cells. However, these adjuvant approaches do not effectively treat the tumor-invaded brain regions due to an intact blood-brain barrier (BBB) that restricts efficient drug penetration or a high risk of toxicity to nearby neural structures. Increasing clinical evidence indicates that the strength of the BBB in protecting brain tumors from exposure to circulating drugs is maintained by not only the intact tight junctions between endothelial cells, but also a broad range of ATP-binding cassette (ABC) drug efflux transporters on endothelial and cancer cells. Our central hypothesis is that sub-cytotoxic photodynamic priming (PDP), which modulates both the tight junction proteins and ABC transporters, can offer a more specific and less disruptive strategy to deliver drugs into the brain tumor effectively. Leveraging cutting-edge nanotechnology, optical imaging and computational modeling, three specific aims will test our hypothesis using orthotopic patient-derived xenograft rat models of glioblastoma. Aim 1 will unravel the molecular impact of nanotechnology-assisted PDP on the tight junction proteins and ABC efflux transporters of brain endothelial cells and cancer cells. Aim 2 will employ fluorescence imaging to monitor nanomedicine delivery and establish a physiologically based pharmacokinetic model. Aim 3 will apply image-based pharmacokinetic modeling to guide the initiation of PDP for bidirectional modulation of drug transport in vivo. Creation of such a pipeline to translate fundamental discoveries into potential therapeutics stands to dramatically accelerate the paradigm shift from standard cytotoxic procedures to a gentler photochemical approach that will revolutionize glioblastoma treatment. The principles and nanotechnology developed here will be adaptable to understanding and treating a broad range of central nervous system disorders, such as neuro-degenerative malignancies and spinal cord disease.
项目总结

项目成果

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Huang Chiao Huang其他文献

Huang Chiao Huang的其他文献

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{{ truncateString('Huang Chiao Huang', 18)}}的其他基金

Targeting Fluid Stress-induced Chemoresistance in a 3D Carcinomatosis Perfusion Model Using Mechanism-based Photo-immunoconjugate Nanoparticles
使用基于机制的光免疫缀合物纳米颗粒在 3D 癌病灌注模型中靶向流体应激诱导的化疗耐药性
  • 批准号:
    10587481
  • 财政年份:
    2023
  • 资助金额:
    $ 20.35万
  • 项目类别:
Nanotherapeutic enhancement of interstitial thermal therapy for glioblastoma
胶质母细胞瘤间质热疗法的纳米治疗增强
  • 批准号:
    10583661
  • 财政年份:
    2022
  • 资助金额:
    $ 20.35万
  • 项目类别:
Addressing Chemoresistance in Pancreatic and Ovarian Cancers: Photodynamic Priming and Repurposing of Tetracyclines using Targeted Photo-Activable Multi-Inhibitor Liposome
解决胰腺癌和卵巢癌的化疗耐药性:使用靶向光激活多抑制剂脂质体进行四环素的光动力启动和再利用
  • 批准号:
    10197327
  • 财政年份:
    2021
  • 资助金额:
    $ 20.35万
  • 项目类别:
Addressing Chemoresistance in Pancreatic and Ovarian Cancers: Photodynamic Priming and Repurposing of Tetracyclines using Targeted Photo-Activable Multi-Inhibitor Liposome
解决胰腺癌和卵巢癌的化疗耐药性:使用靶向光激活多抑制剂脂质体进行四环素的光动力启动和再利用
  • 批准号:
    10373082
  • 财政年份:
    2021
  • 资助金额:
    $ 20.35万
  • 项目类别:
Addressing Chemoresistance in Pancreatic and Ovarian Cancers: Photodynamic Priming and Repurposing of Tetracyclines using Targeted Photo-Activable Multi-Inhibitor Liposome
解决胰腺癌和卵巢癌的化疗耐药性:使用靶向光激活多抑制剂脂质体进行四环素的光动力启动和再利用
  • 批准号:
    10594035
  • 财政年份:
    2021
  • 资助金额:
    $ 20.35万
  • 项目类别:
Photodynamic Priming for Bidirectional Modulation of Drug Transport Across the Blood-Brain Tumor Barrier
光动力引发双向调节药物跨血脑肿瘤屏障转运
  • 批准号:
    10197928
  • 财政年份:
    2020
  • 资助金额:
    $ 20.35万
  • 项目类别:
Photodynamic Priming for Bidirectional Modulation of Drug Transport Across the Blood-Brain Tumor Barrier
光动力引发双向调节药物跨血脑肿瘤屏障转运
  • 批准号:
    10381605
  • 财政年份:
    2020
  • 资助金额:
    $ 20.35万
  • 项目类别:
Multifunctional, GBM-activatable nanocarriers for image-guided photochemotherapy
用于图像引导光化疗的多功能、GBM 可激活纳米载体
  • 批准号:
    9260692
  • 财政年份:
    2016
  • 资助金额:
    $ 20.35万
  • 项目类别:

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  • 批准号:
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