OTHER FUNCTIONS "TARGET SPECIFIC AND DRUG LOADED IRON OXIDE NANOPARTICLES FOR CA

其他功能“针对CA的特定目标和载药氧化铁纳米颗粒

• 批准号: 8564318
• 负责人: ANDREW WANG
• 金额: $ 120万
• 依托单位: OCEAN NANOTECH, LLC
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-28 至 2014-09-27
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8564318
• 关键词: Adjuvant Therapy; Affinity; Animal Model; Animals; Biodistribution; Breast Cancer Cell; Cancer Etiology; Cancer Patient; Cessation of life; Clinical Trials; Combination Drug Therapy; Detection; Disease; Dose; Doxorubicin; Drug Delivery Systems; Drug Kinetics; Endocytosis; Engineering; Environment; Future; Goals; Human; Investigation; Lesion; Ligands; Magnetic Resonance Imaging; Magnetism; Methods; Modeling; Mus; Neoplasm Metastasis; Oryctolagus cuniculus; Patients; Pharmaceutical Preparations; Pharmacodynamics; Phase; Postoperative Period; Primary Neoplasm; Production; Quality Control; Resistance development; Second Primary Cancers; Site; Small Business Innovation Research Grant; Testing; Therapeutic; Toxic effect; Translating; Treatment Efficacy; Woman; Xenograft Model; activating transcription factor; cancer type; chemotherapeutic agent; chemotherapy; commercialization; density; effective therapy; improved; iron oxide; large scale production; malignant breast neoplasm; nanodrug; nanoparticle; neoplastic cell; novel strategies; phase 1 study; preclinical study; response; success; theranostics; tumor; uptake

Breast cancer is the most common type of cancer and the second leading cause of cancer death among women with more than one million new cases and 370,000 deaths worldwide yearly. Chemotherapy drugs, such as Doxorubicin, have been used in both pre- and post-operative adjuvant therapy or as the main therapeutic option for breast cancer patients with metastatic disease. Although recent advances in the combination of chemotherapy drugs have improved survival for breast cancer patients, a high percentage of patients develop resistance to chemotherapeutic agents and fail treatment. Therefore, novel approaches for the effective treatment of breast cancer are urgently needed to improve the therapeutic response. This project aims to develop a Doxorubicin loaded and target specific magnetic iron oxide nanoparticle (IONP) platform for targeted therapy of breast cancer. The proposed nanodrug can be systemically delivered and selectively accumulated at the primary and metastatic tumor sites and subsequently internalized into breast cancer cells via endocytosis. Selective enrichment of the IONP in tumor cells and the tumor environment produces strong MRI contrast for the detection of drug delivery and response in the tumor lesions by MR imaging. After demonstration of the feasibility that the engineered nanodrug can target the tumor in an animal model, the goal of this SBIR Phase II project is to extend the investigation of the successes in the Phase I study and move closer to translating this platform into preclinical trials and commercialization by further optimizing the targeted theranostic nanodrug platform for efficacy, biodistribution, toxicity, pharmacokinetics/pharmacodynamic studies, and future clinical trials.

乳腺癌是最常见的癌症类型，也是妇女癌症死亡的第二大原因，全世界每年有100多万新病例和37万人死亡。化疗药物，如阿霉素，已被用于术前和术后辅助治疗，或作为转移性乳腺癌患者的主要治疗选择。尽管化疗药物联合治疗的最新进展提高了乳腺癌患者的生存率，但仍有很高比例的患者对化疗药物产生耐药性并导致治疗失败。因此，迫切需要新的有效治疗乳腺癌的方法来提高治疗效果。本项目旨在开发一种负载多柔比星的靶向特异性磁性氧化铁纳米粒子（IONP）平台，用于乳腺癌的靶向治疗。所提出的纳米药物可以系统递送并选择性地积聚在原发和转移性肿瘤部位，随后通过内吞作用内化到乳腺癌细胞中。肿瘤细胞和肿瘤环境中IONP的选择性富集产生强烈的MRI对比，通过MRI成像检测肿瘤病变中的药物传递和反应。在证明了工程纳米药物可以在动物模型中靶向肿瘤的可行性之后，SBIR二期项目的目标是通过进一步优化靶向治疗纳米药物平台的疗效、生物分布、毒性、药代动力学/药效学研究和未来的临床试验，扩大对一期研究成功的调查，并将该平台转化为临床前试验和商业化。