新型纳米囊泡的构建并用于癌症诊断和治疗的研究

Vesicles have been a hot subject of research because of their applications in a variety of different areas reaching from models of biological membranes, agents for drug/gene delivery, and microreactors for the production of inorganic materials to the preparation of nanomaterials. However, the materials employed for construction of vesicles are usually either not easily available or expensive and require multi-step synthesis, which has greatly impeded the high throughput construction and screening of novel vesicles. Based on the research status of the ionic vesicle, this proposal focuses on development of new strategies for efficient and green synthesis of N-containing onium salts in effort to establish a library of onium salts. Following the strategy of counterion-induced vesicle formation, different types of monodispersed and multifunctional nanovesicles will be obtained on basis of the onium salts library and a deeper understanding of the counterion-induced strategy is expected to be disclosed. Meanwhile, a series of properties including MR and fluorescence imaging and smart delivery of gene and drug are designed for target nanovesicles, which would offer a promising application in the cancer diagnosis and therapy.

囊泡在生物膜仿生、药物和基因传输、无机材料的微反应器以及纳米材料制备等众多领域均得到广泛的应用。现有构筑囊泡的材料普遍存在结构复杂、合成困难以及价格昂贵等缺点，从而极大地限制了囊泡体系的高通量构建和性能筛选。本项目基于目前离子型功能囊泡的研究现状，拟发展氮鎓盐高效绿色的合成新方法，构建鎓盐分子库，为构建功能多样的纳米囊泡体系提供化学基础。同时，利用抗衡离子诱导形成囊泡的策略，制备并筛选尺寸单一、性能优异的纳米囊泡，并深入研究基于抗衡离子诱导的离子型纳米囊泡的构建机制，为今后离子型囊泡的构筑提供强有力的理论基础。此外，基于巧妙的分子设计，赋予目标囊泡体系磁共振显影、荧光成像及药物和基因在肿瘤细胞环境下的智能释放等一系列功能，开发它们在癌症诊断及抗癌药物和基因传输中的应用。

癌症已成为一种严重威胁人类生命的恶性疾病，开发更为有效的新型诊疗系统已成为预防及治疗癌症亟需解决的重要难题之一。本项目基于目前癌症诊断和治疗的研究现状，构建同时具备聚集诱导发光及双光子荧光成像性能和多重肿瘤微环境刺激响应下的药物可控释放功能的纳米药物载体，实现癌症的诊断和治疗。本项目取得的主要进展如下：1、构建具有聚集诱导发光性能的新型双光子荧光分子库，为今后用于癌症诊断的新型纳米药物载体的构筑提供坚实的研究基础；2、利用抗衡离子的诱导作用，实现纳米囊泡的制备，为构建功能多样的纳米囊泡体系提供化学基础；3、利用目标鎓盐分子优异的生物成像能力，为癌症诊断和纳米载体在体内传输的实时监测提供基础；4、构筑肿瘤微环境相应的纳米药物载体，有效提高了纳米药物载体的稳定性，同时实现抗癌药物的智能可控释放，提高纳米药物载体的抗癌能力和降低抗癌药物的毒副作用；5、同时赋予纳米药物载体聚集诱导发光及双光子荧光成像性能和多重肿瘤微环境刺激响应下的协同智能药物可控释放功能，实现癌症的诊疗一体。