Nanoplatform-based combinational therapy against breast cancer

基于纳米平台的乳腺癌联合疗法

• 批准号: 8335496
• 负责人: Jin Xie
• 金额: $ 24.15万
• 依托单位: UNIVERSITY OF GEORGIA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8335496
• 关键词: ABCB1 gene; Abraxane; Accounting; Address; Amines; Chemotherapy-Oncologic Procedure; Complex; Doxorubicin; Drug Delivery Systems; Drug Kinetics; Drug resistance; Extravasation; Genes; Human; Investigation; Lead; Ligand Binding; Malignant Neoplasms; Nanoconjugate; Paclitaxel; Pharmaceutical Preparations; Regimen; Serum Albumin; Site; Small Interfering RNA; Tariquidar; Therapeutic; Therapeutic Agents; Therapeutic Effect; Time; Treatment Efficacy; base; cancer stem cell; cancer therapy; cell killing; chemotherapeutic agent; improved; inhibitor/antagonist; iron oxide; killings; magnetic field; malignant breast neoplasm; meetings; nanoparticle; neoplastic cell; novel; novel strategies; salinomycin; success; tumor

Among the obstacles to successful breast cancer chemotherapy, three have been critical: problems of drug delivery, drug resistance, and cancer stem cells (CSCs). Until now, no effort has been made to address all three issues in a single approach. This proposal seeks to meet the challenge through a nanoplatform that we recently developed, which is comprised of a human serum albumin (HSA) coating, an amine-rich intermediate coating, and an iron oxide nanoparticle (lONP) core. It structurally resembles Abraxane, a commercial paclitaxel-HSA complex, but has smaller hydrodynamic size therefore better tumor accumulation rate and extravasation rate. Such favorable pharmacokinetics can be further improved by adding an external field at the tumor sites, making the nanoplatform a promising drug delivery vehicle. With superior ligand binding capability afforded by both the outer HSA and intermediate amine-rich layers, such nanoplatform can load a broad range of drug molecules. In this proposal, we plan to load such a nanoplatform with doxorubicin (or paclitaxel), salinomycin and tariquidar (or siRNA that targets the MDR-1 gene). Doxorubicin (or paclitaxel) is a chemotherapeutic agent that is commonly used in breast cancer therapy, directed toward killing the differentiated tumor cells that account for most of a tumor mass. Salinomycin is a recently identified therapeutic agent with selective CSC killing capability. Both tariquidar and siRNA can function as MDR-1 inhibitors and their modulating effects may lead to increased drug accumulation. It is hoped that, with complementary cancer killing mechanisms and favorable tumor targeting profile provided by the nanoplatform, this novel approach may lead to dramatically improved therapeutic effects. This will be the first investigation on tumor therapy to address problems of drug delivery, drug resistance, and CSCs in a single approach. Success of this study may be a milestone in breast cancer therapy for providing a powerful, all-inone, breast cancer therapeutic regimen.

在成功的乳腺癌化学疗法的障碍中，三种至关重要：药物问题 递送，耐药性和癌症干细胞（CSC）。到目前为止，还没有努力解决所有问题 单个方法中的三个问题。该提议旨在通过我们 最近开发的，由人类血清白蛋白（HSA）涂层组成，这是一种胺丰富的胺 中间涂层和氧化铁纳米颗粒（LONP）核心。它在结构上类似于Abraxane，一个 商业紫杉醇-HSA复合物，但具有较小的流体动力大小，因此肿瘤积累更好 速率和外部率。通过添加外部 在肿瘤部位田地，使纳米植物成为有前途的药物。具有上级配体 外部HSA和中间胺富含层的绑定能力，这种纳米平台可以 加载广泛的药物分子。在此提案中，我们计划用阿霉素加载这样的纳米板。 （或紫杉醇），盐霉素和塔基动物（或针对MDR-1基因的siRNA）。阿霉素（或紫杉醇） 是一种化学治疗剂，通常用于乳腺癌疗法，用于杀死 分化的肿瘤细胞解释了大多数肿瘤质量。盐霉素是最近确定的 具有选择性CSC杀死能力的治疗剂。塔基动物和siRNA都可以用作MDR-1 抑制剂及其调节作用可能导致药物积累增加。希望有 补充癌症的杀戮机制和有利的肿瘤靶向特征 纳米文化，这种新型方法可能会导致大幅改善治疗作用。这将是第一个 研究肿瘤疗法以解决单个药物输送，耐药性和CSC问题的研究 方法。这项研究的成功可能是乳腺癌疗法的里程碑 乳腺癌治疗方案。