Novel pRNA Nanoparticle Delivery as Directed Therapy for Colorectal Cancer Metastasis

新型 pRNA 纳米颗粒递送作为结直肠癌转移的定向治疗

基本信息

  • 批准号:
    9547788
  • 负责人:
  • 金额:
    $ 28.04万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2015
  • 资助国家:
    美国
  • 起止时间:
    2015-09-25 至 2020-08-31
  • 项目状态:
    已结题

项目摘要

 DESCRIPTION (provided by applicant): Although progress has been made in survival of patients with earlier stage colorectal cancer (CRC), only minimal improvement has been noted in patients with systemic metastases (Stage IV disease). Current chemotherapeutic agents, while highly effective at killing CRC cells, are limited by their systemic toxicity. If advances ar to be made in the survival of cancer patients, highly innovative strategies are required for more targeted delivery of anti-cancer agents directly to CRC metastases. Our ultimate translational goal is to develop a highly effective and less toxic approach to specifically deliver anti-cancer agents to CRC metastases. To achieve this goal, we have assembled a multidisciplinary and highly collaborative team who are at the forefront of molecular signaling pathways in CRC, CRC treatment modalities, medicinal chemistry, novel nanoparticle synthesis and delivery systems. Over the last two years, we have made significant progress to achieve our goals: (i) using a novel three-way junction (3WJ) motif, we have constructed thermodynamically and chemically stable three-branched RNA nanoparticles with an aptamer against receptors that can deliver a small molecule inhibitor or chemotherapeutic agent specifically to CRC metastases in the liver, (ii) we have constructed a variety of RNA nanoparticles using the pRNA-3WJ motif as a scaffold and have demonstrated in critical experiments that the resulting RNA constructs retained their folding and independent functionalities for specific cell binding, cell entry and cancer targeting, both in vitro and in vivo, (iii) we have shown that the RNA nanoparticles remain intact after systemic injection into mice and strongly bind to tumors with little accumulation in normal organs or tissues; these RNA constructs are non- toxic, non-immunogenic, and display favorable pharmacological profiles in mice, and (iv) we have demonstrated localized in vivo delivery of pRNA-3WJ to CRC xenografts and liver metastases. Thus, the central hypothesis of our proposal is that CRC receptor-specific delivery of chemotherapeutic agents using our pRNA-3WJ nanoparticles will provide a safe, effective strategy to selectively target and inhibit CRC metastasis. To address our hypothesis, we have designed experiments with the following Specific Aims: 1) to construct pRNA-3WJ nanoparticles coupled with anti-cancer agents and analyze their stability, cellular uptake and anti-proliferative effects in vitro; 2) to determine te pharmacokinetics, stability, safety and drug delivery of pRNA-drug conjugates in vivo; and 3) to evaluate the selective delivery and in vivo anti-tumor effect of pRNA- 3WJ nanoparticles coupled with anti-cancer agents. In summary, our enthusiasm for our current proposal is driven not only by its inherent scientific importance, but also by its translational potential, clinical impact, and the possibility to provide a more effective and less toxic delivery system targeting CRC metastases.


项目成果

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Bernard Mark Evers其他文献

Bernard Mark Evers的其他文献

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{{ truncateString('Bernard Mark Evers', 18)}}的其他基金

Targeting the Immunosuppressive Tumor Microenvironment for Colorectal Cancer Treatment
针对结直肠癌治疗的免疫抑制肿瘤微环境
  • 批准号:
    10748123
  • 财政年份:
    2023
  • 资助金额:
    $ 28.04万
  • 项目类别:
Appalachian Career Training in Oncology (ACTION) Program
阿巴拉契亚肿瘤学职业培训 (ACTION) 计划
  • 批准号:
    10245140
  • 财政年份:
    2018
  • 资助金额:
    $ 28.04万
  • 项目类别:
Appalachian Career Training in Oncology (ACTION) Program
阿巴拉契亚肿瘤学职业培训 (ACTION) 计划
  • 批准号:
    10001327
  • 财政年份:
    2018
  • 资助金额:
    $ 28.04万
  • 项目类别:
Appalachian Career Training in Oncology (ACTION) Program
阿巴拉契亚肿瘤学职业培训 (ACTION) 计划
  • 批准号:
    10475257
  • 财政年份:
    2018
  • 资助金额:
    $ 28.04万
  • 项目类别:
Altered Lipid Metabolism as a Novel Target for Colon Cancer Treatment
改变脂质代谢作为结肠癌治疗的新目标
  • 批准号:
    10227741
  • 财政年份:
    2017
  • 资助金额:
    $ 28.04万
  • 项目类别:
Mechanisms regulating neurotensin secretion and function
调节神经降压素分泌和功能的机制
  • 批准号:
    9219942
  • 财政年份:
    2017
  • 资助金额:
    $ 28.04万
  • 项目类别:
Mechanisms Regulating Neurotensin Secretion and Function
调节神经降压素分泌和功能的机制
  • 批准号:
    10536470
  • 财政年份:
    2017
  • 资助金额:
    $ 28.04万
  • 项目类别:
Mechanisms Regulating Neurotensin Secretion and Function
调节神经降压素分泌和功能的机制
  • 批准号:
    10651886
  • 财政年份:
    2017
  • 资助金额:
    $ 28.04万
  • 项目类别:
Novel pRNA Nanoparticle Delivery as Directed Therapy for Colorectal Cancer Metastasis
新型 pRNA 纳米颗粒递送作为结直肠癌转移的定向治疗
  • 批准号:
    9753735
  • 财政年份:
    2015
  • 资助金额:
    $ 28.04万
  • 项目类别:
Cancer specific and organ-avoiding RNA architectures for quantitative imaging
用于定量成像的癌症特异性和器官回避 RNA 结构
  • 批准号:
    9208386
  • 财政年份:
    2014
  • 资助金额:
    $ 28.04万
  • 项目类别:

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口服抗肿瘤药物的获取延迟
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