Development of drug-loaded antibody-targeted nanoparticles to kill colorectal cancer cells

开发载药抗体靶向纳米粒子来杀死结直肠癌细胞

• 批准号: nhmrc : 433613
• 负责人: A/Pr Joan Heath
• 金额: $ 34.22万
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2007
• 资助国家: 澳大利亚
• 起止时间: 2007-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/development-drug-loaded-cancer-cells/78059
• 关键词: Development; drug; loaded; antibody; targeted

COLORECTAL CANCER (CRC) is the most common cancer in the Western world. In Australia, the five-year survival rate after surgical resection of the primary lesion is 55%, and for patients with advanced disease the five-year survival rate is less than 10%. Colorectal cancer is relatively resistant to radiotherapy and chemotherapy and therefore there is great emphasis on identifying alternative modes of treatment. One approach that is attracting considerable attention is IMMUNOTHERAPY. In particular, the A33 ANTIBODY system appears to have the potential to target colorectal cancer cells and achieve therapeutic outcomes. The A33 system has been well characterised in both a clinical and laboratory setting over the last few years and recent clinical trials with humanised versions of the A33 antibody have demonstrated rapid localisation and accumulation of radiolabelled A33 to colorectal cancer lesions. The application of NANOTECHNOLOGY to biological systems is likely to transform the way we treat a variety of diseases over the course of the next decade. Nanosized drug delivery vehicles have the potential to revolutionise the treatment of a number of diseases, cancer in particular. Hollow capsules can be synthesised with a drug sequestered inside the capsule, where the capsule wall performs a dual role of protecting the body from potentially harmful side effects of the drug, as well as protecting the drug from being degraded by the body. We plan to use these nanosized drug carriers, functionalised with the A33 antibody, to deliver chemotherapy agents directly to the colorectal cancer cells. We have recently demonstrated that in vitro, nanocapsules functionalised with the A33 antibody specifically bind to CRC cells, and once bound, the capsules are internalised. In this proposal we will test the ability of these particles to kill CRC cells in mice harbouring human tumours.

结直肠癌（CRC）是西方世界最常见的癌症。在澳大利亚，手术切除原发病灶后的五年生存率为55%，晚期患者的五年生存率不到10%。结直肠癌对放疗和化疗相对耐药，因此非常重视确定替代治疗模式。其中一个引起广泛关注的方法是免疫治疗。特别是，A33抗体系统似乎具有靶向结直肠癌细胞并实现治疗结果的潜力。在过去几年中，A33系统已在临床和实验室环境中得到很好的表征，最近使用人源化A33抗体的临床试验已证明放射性标记的A33在结直肠癌病变中快速定位和积累。纳米技术在生物系统中的应用可能会在未来十年内改变我们治疗各种疾病的方式。纳米药物载体有可能彻底改变许多疾病的治疗，特别是癌症。中空胶囊可以合成为胶囊内隔离的药物，其中胶囊壁起到保护身体免受药物的潜在有害副作用以及保护药物免受身体降解的双重作用。我们计划使用这些纳米药物载体，用A33抗体功能化，将化疗药物直接递送到结直肠癌细胞。我们最近已经证明，在体外，用A33抗体功能化的纳米胶囊特异性结合CRC细胞，并且一旦结合，胶囊就被内化。在这项提案中，我们将测试这些颗粒杀死携带人类肿瘤的小鼠中CRC细胞的能力。