Dual Targeted Nanoparticle therapy for Glioblastoma Multiforme

多形性胶质母细胞瘤的双靶向纳米颗粒治疗

基本信息

批准号：
8634460
负责人：
Randal Singh Goomer
金额：
$ 22.5万
依托单位：
AVRYGEN CORPORATION
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-06-04 至 2015-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8634460
关键词：
Adult Affect Amino Acids Animal Model Automobile Driving Binding Biological Assay Blood - brain barrier anatomy Cell Line Cell Proliferation Cell physiology Cells Chlorotoxin Clinical Trials Data Development Disease Down-Regulation Drug Delivery Systems Drug Formulations Ensure Excision Fluorescent Dyes Genes Glioblastoma Glioma Goals Growth Home environment Human Immunologic Surveillance Injection of therapeutic agent Intervention Ligands Location Longitudinal Studies Lysine MET Oncogene Malignant Neoplasms Matrigel Invasion Assay Measurement Measures Mediating Mediator of activation protein Methods Molecular Molecular Target Operative Surgical Procedures Outcome Study Patients Peptides Persons Phase Play Population Porifera Primary Brain Neoplasms Protons Publishing RNA Interference Radiation therapy Recurrence Repression Resistance Resistance development Role Scorpion Venoms Signal Pathway Small Interfering RNA Stem cells Surface Tail Testing Therapeutic Time Tissues Transcript Transferrin Treatment Efficacy Tumor Burden Tumor Cell Invasion Veins base cancer cell cancer recurrence chemotherapy design in vitro testing in vivo mouse model nanoparticle neoplastic cell new therapeutic target novel outcome forecast phase 2 study pre-clinical public health relevance scaffold self-renewal stem success therapeutic siRNA trafficking tumor tumor progression uptake zeta potential

项目摘要

DESCRIPTION (provided by applicant): Glioblastoma Multiforme is a lethal cancer with devastating prognosis. Glioblastoma affects 5-8 persons per 100,000 population. Even using the most aggressive therapeutic approaches, which include, surgical resection of tumor mass, radiation therapy and chemo intervention, median survival term is less than 15-months. The high recurrence of this cancer is due to remnant reservoir of stem cells (Glioma Stem Cells: GSC) that renew the tumor after resection. Therefore, there is urgent unmet need to develop novel targeted therapeutics for Glioblastoma that target critical molecular mediators in its reservoir of stem like cells. Results of our preliminary studies drive this proposal. In preliminar studies, we have formulated novel stabilized and targeted nanoparticles for delivery of dual disease specific siRNAs to Glioblastoma stem like cells. Our nanoparticles carry specific targeting moieties that can readily cross the blood brain barrier and home-in to Glioblastoma cells. Using these nanoparticles we propose to deliver siRNAs to repress molecular mediators critical for tumor progression and self-renewal. Use of siRNA to target most critical mediators expressed in GBM stem like cells ensures reduction of tumor burden to increase patient survival. The dual targeted Nanoparticle therapeutics will be tested in our mouse model of primary human Glioblastoma. Completion of this Phase I preclinical proposal would successfully advance toward Phase II, with the final goal of initiating a clinical trial for patients with Glioblastoma.

描述（由申请人提供）：多形胶质母细胞瘤是一种具有毁灭性预后的致命癌。胶质母细胞瘤影响每100,000人口5-8人。即使使用最具侵略性的治疗方法，其中包括肿瘤肿块的手术切除，放射治疗和化学干预，中位生存期限也小于15个月。该癌症的高复发是由于干细胞（神经胶质瘤干细胞：GSC）的残留储层引起的，它们在切除后更新了肿瘤。因此，迫切需要开发针对胶质母细胞瘤的新型靶向疗法，该治疗剂靶向其在茎（例如细胞）中的关键分子介质。我们的初步研究的结果推动了这一建议。在前研究中，我们已经制定了新颖的稳定和靶向纳米颗粒，用于将特定于双重疾病的siRNA传递到胶质母细胞瘤茎（如细胞）中。我们的纳米颗粒具有特定的靶向部分，可以轻松地穿越血脑屏障并归根于胶质母细胞瘤细胞。使用这些纳米颗粒，我们提议提供siRNA，以抑制对肿瘤进展和自我更新至关重要的分子介质。使用siRNA来瞄准在GBM茎中表达的大多数关键介质，例如细胞，可确保减少肿瘤负担以增加患者的生存率。双重靶向纳米颗粒疗法将在我们的原代人胶质母细胞瘤模型中进行测试。该阶段I临床前建议的完成将成功迈向II期，最终目标是针对胶质母细胞瘤患者进行临床试验。