核酸适配体-DNA纳米凝胶药物载体的构建及其肿瘤靶向治疗研究

One of the key contents for tumor targeted therapy is the design and synthesis of smart drug carrier with high specificity and high efficacy. In this project, by combining of molecular engineering technology, assembly of functional nanomaterials and nucleic acid, cell biology and in vivo imaging, a series of aptamer mediated DNA hydrogels will be developed as excellent carrier for drug delivery and tumor targeted therapy. Aptamer and DNA hydrogels will render this drug carrier with high targeted cell binding ability and excellent drug carry ability. By choosing liver cancer cell and tumor in living body as study objects, some novel tumor therapy technologies, including combining targeted therapy, smart responsive nanocarrier for drug release, theranostics will be adopted into aptamer-DNA hydrogel mediated tumor targeted therapy. This study holds great promise to provide new methods and technologies for the drug delivery and therapy of cancer. And this project is also an innovative subject that is expected to promote the development of modern analytical chemistry and tumor medicine in the cross field of molecular engineering and biological nanotechnology.

设计与合成高靶向与高疗效的纳米药物载体是肿瘤靶向治疗技术研究的关键内容之一。本项目结合分子工程技术、纳米生物技术、材料组装技术、细胞生物学、活体成像技术等交叉学科与前沿技术，基于核酸适配体的特异性肿瘤靶向识别能力和DNA纳米凝胶的高效药物转载能力，设计和构建新型靶向型DNA纳米凝胶药物载体；选择肝癌作为主要靶标对象，实现药物的高效传递与肿瘤的靶向治疗作用；并且进一步构建智能药物可控释放体系，发展肿瘤的联合靶向治疗体系和“诊疗一体化”体系，为药物传递、肿瘤靶向治疗、以及药物研发等提供技术平台。这将是一项在分子工程技术和生物纳米技术等前沿交叉领域推动现代分析化学与肿瘤医学发展的创新性课题。

本项目以肿瘤的靶向治疗为目的，利用核酸适配体的特异性肿瘤识别能力和DNA的高效药物转载能力，设计和构建新型靶向型DNA纳米药物载体。主要成果包括：1) 发展了基于DNA的纳米载体，实现了生物酶与药物分子的高效负载与转运；2) 制备和合成了不同性能的功能纳米材料，用于纳米药物载体的构建；3) 基于核酸适配体的靶向识别功能，发展了新型生物分析与肿瘤细胞检测方法；4) 结合不同的响应基元，发展了基于DNA和纳米载体的可控响应体系；5) 组合不同的治疗模式，发展了基于DNA和纳米载体的肿瘤杀伤应用平台。通过该项目，发表SCI学术论文26篇，会议论文7篇，申请/授权发明专利2项，培养毕业10名研究生。该项目为药物传递、肿瘤靶向治疗、以及药物研发等研究提供了技术平台。该项目也拓展了基于DNA-纳米载体的肿瘤医学应用研究以及细胞与活体层面的成像研究，拓展了基于核酸适配体在生物医学工程领域的更深层次发展做出贡献，并为智能生物材料和逻辑纳米器件的研究提供重要参考作用。