“分子胶囊”型自由基发生器用于深层乏氧肿瘤治疗

Tumor hypoxia is an important reason for the difficulty in curing cancer and its recurrence. Efficiently and accurately killing the deep hypoxic cancer cells has become the hot topic and frontier in the research of cancer treatment. This project intends to build a “molecular capsule” type free radical generator for the treatment of deep hypoxic tumor. Based on the host-guest interaction of free radical initiator 2,2'-azobis[2-methyl-N-(2-aminoethyl)propionamide] (ABEA) and cucurbit[7]uril (CB[7]), ABEA is encapsulated into the cavity of CB[7] to form the “molecular capsule”, at the same time, the free radical generation ability of ABEA is also inhibited. By using a hypoxic sensitive nanovesicle (NV) as the drug carrier, ABEA@CB[7]@NV is prepared. In cancer treatment, ABEA@CB[7]@NV can selectively release the “molecular capsule” in hypoxic tumor region. Due to its small size (about 2 nm), the “molecular capsule” can efficiently penetrate into the deep tumor. When ABEA@CB[7] enters to tumor cells, its host-guest interaction can be affected by intracellular substances and be activated, then ABEA decomposes to generate free radicals, and efficiently and accurately kills the deep hypoxic cancer cells. This project provides a new method to effectively kill the hypoxic cancer cell in deep tumor, which exhibits important research value.

肿瘤乏氧是癌症治疗难治愈、易复发的重要原因。高效精准地杀灭肿瘤深层乏氧细胞，已成为癌症治疗研究的重点和前沿。本项目拟构建“分子胶囊”型自由基发生器用于深层乏氧肿瘤治疗。拟利用自由基引发剂偶氮二异(N-胺乙基)丁脒(ABEA)与葫芦[7]脲(CB[7])的主客体作用，将ABEA包裹在CB[7]的空腔中，形成“分子胶囊”ABEA@CB[7]，并抑制ABEA的自由基产生能力。进一步利用乏氧敏感型纳米囊泡(NV)作为药物载体，制备ABEA@CB[7]@NV。在肿瘤治疗中，ABEA@CB[7]@NV可在乏氧肿瘤区域选择性释放“分子胶囊”。“分子胶囊”尺寸小巧(约2 nm)，可以实现对肿瘤组织的高效渗透。当“分子胶囊”进入肿瘤细胞后，其主客体作用可被细胞内物质破坏，实现自激活的效果并产生自由基，达到高效精准地杀伤深层乏氧肿瘤细胞的效果。本项目为深层乏氧肿瘤治疗提供了新的手段，具有重要研究价值。

肿瘤乏氧是癌症治疗难治愈、易复发的重要原因。高效精准地杀灭肿瘤深层乏氧细胞，已成为癌症治疗研究的重点和前沿。基于此本项目设计并制备了一系列基于自由基及其超分子自组装的多功能纳米药物，依据自由基的治疗功能和超分子自组装的调控性能克服肿瘤治疗中存在的关键问题。包括：设计“超分子型自由基发生器”，通过主客体作用调剂自由基产生能力，为解决光动力学疗法对氧气的依赖问题开辟了新的途径，并对该领域进行了综述性报道；设计基于葫芦脲的超分子光敏剂、超分子有机框架材料等用于肿瘤的光动力学治疗，通过主客体作用实现了光敏剂光动力学效果的可逆调控；设计了基于离液效应构建含自由基超分子有机框架材料用于光热治疗等。本项目已完成预定研究目标，通过各类自由基的构建和超分子自组装，构建了一系列新型纳米药物，为解决肿瘤治疗过程中乏氧等问题，实现肿瘤的精准个性化治疗提供了新的思路和见解。在本项目资助下，本项目申请人以一作或通讯作者身份在Adv. Funct. Mater.、Small.、Biomaterials等国际顶级杂志上发表学术论文7篇，申请中国发明专利3项，培养硕士研究生3名。