肿瘤微环境原位构筑纳米载体及其用于药物递送的研究

Although nanomaterials as drug carriers have been used for improving the tumor therapy，they did not achieved the tumor therapy with high efficiency and low toxicity. In situ self-assembly of supramolecules in vivo developed by our group showed long time retention of nanomaterials in tumor site, which support a new way for carriers’ design. In this project, the new type nanocarriers with morphology transformation from nanoparticles to nanofibers in the tumor microenvironment will be designed to enhance the long time retention. The nanofibers as host are in situ constructed in the tumor microenvironment to home drug molecules as guest, which will be expected to improve the concentrations of drug in tumor and decrease the side effect such as liver and spleen burden by traditional drug delivery. The project will explore that the morphology transformation law and mechanism and how the host-guest interaction affected drug enrichment and delivery, which provides ideas for developing new methods of tumor treatment.

纳米材料作为小分子药物的载体提升了肿瘤治疗效果，仍然未能实现肿瘤治疗的高效低毒。我们采用在体内原位构筑超分子组装体的方法，显著提升了纳米材料在病变部位的富集滞留，为设计新载体、探索肿瘤治疗的新方法奠定了基础。本项目拟原位构筑小分子药物的载体，采用“两步法”给药，以实现肿瘤治疗的高效低毒。两步法具体内容如下：一、原位构筑作为主体的药物载体：拟设计肿瘤微环境敏感的多肽纳米颗粒，在肿瘤区域由纳米颗粒转化组装形成纳米纤维，结合纳米颗粒具有的EPR效应和原位构筑组装体具有的滞留效应，实现材料的高效转化，长效滞留；二、载体富集客体小分子药物：通过纳米纤维载体与小分子药物的主-客体相互作用，以实现小分子药物的高效富集，降低传统载药方法所引起的肝肾负担。探索多肽纳米材料微环境响应下的形貌转化规律，及转化机理，揭示主-客体相互作用对药物富集释放的影响规律，为发展肿瘤治疗的新方法提供思路。

癌症是具有发病率高，死亡率高的特点，称为公共卫生的面临的重要问题。纳米材料作为小分子药物的载体可有效改善小分子药物的递送，降低系统毒性，但是仍然不能实现高效低毒。本项目针对这一问题，探索了体内原位构筑超分子组装体的方法，设计了肿瘤微环境敏感的多肽纳米颗粒，其在肿瘤区域由纳米颗粒原位转化组装形成纳米纤维，纳米颗粒可以通过EPR作用和主动靶向作用富集在肿瘤区域，形成的纳米纤维可以在肿瘤部位长时间滞留，这种形成的纳米纤维网络可以用于小分子药物的富集。我们探索了纳米材料的形貌调控行为与机制，考察了纳米材料与小分子药物之间的相互作用。这种递送方法为有效的设计药物的递送提供了研究基础的技术参考。