肿瘤微波热疗增敏剂――纳米生物膜配质体制备研究

It is a critical microwave hyperthermia problem to solve the heating tumor tissue up at 43-45 ℃ for a period without irreversibly damaging the normal tissues around the tumor in clinical medicine. This proposal aims to develop one kind of self-assemble targeted nanoparticles, biomembrane liposome complex, in “one-pot” method and by using biomaterials approved by FDA or CFDA, for instance, lecithin, albumin, human essential elements iron, and targeting peptides. The research mainly focuses on testing the stability and structure characterize of liposome complex, the law of thermal transition, and tumor cellular targeting experiments. Furthermore, this proposal intends to monitor the temperature rising process of tissue accumulated area with liposome complex by microwave radiated and measure the microwave dielectric property. This proposal has important scientific meaning and practical value in helping overcome the non-target problem during the superficial or deep-seated tumor hyperthermia process.

肿瘤微波热疗中，如何控制肿瘤组织升高到43－45℃,并保持一定的时间，又不引起附近正常组织的不可逆损伤，是临床上急需解决的难题。本课题拟用FDA或CFDA批准的磷脂、白蛋白等生物材料、靶向多肽和人体必需元素铁为配位中心，一锅法自组装成纳米靶向生物膜配质体(简称配质体)。重点进行配质体稳定性研究，结构表征，微波热转化规律研究，肿瘤细胞靶向实验研究。拟实现仿体中配质体受微波激发升温过程中的温度监控，以及介电特性的测量。达到热疗过程中既能最大限度地破坏癌症组织，又尽可能不损伤正常的组织目的。这对克服目前热疗作用表浅、深部肿瘤加热无选择性的难题具有重要的科学意义。

中国常见的恶性肿瘤多为深部肿瘤。如何提高光热、光动力治疗的深度、增加靶向，研发有效除清深层组织中的实体瘤及扩散的细胞的光动力治疗方法成为当前研究的热点。本课题通过添加成孔剂来制备基于金属氧化物的多孔陶瓷材料，采用超疏水材料原位水热浸渍法及固化后制备了超疏水纳米配质制备装置。用FDA或CFDA批准的磷脂、白蛋白等生物材料，人体必需元素铁为配位中心，结合已经筛选出的靶向多肽组装成高介电常数的纳米靶向载体(简称纳米配质体)。以低成本的微波作为激发源，照射进入肿瘤组织的配质体，使肿瘤组织快速升高温度到43-45℃的肿瘤热疗范围。结果表明该技术升温速度快、热疗效果好，只需要几个疗程就可以缩小或清除扩散的肿瘤细胞，达到热疗过程中既能最大限度地破坏癌症组织，又尽可能不损伤正常的组织目的。该技术研发出一种比脂质体更加稳定、不含胆固醇的通用纳米囊泡载体—纳米生物膜配质体，对克服目前热疗作用表浅、深部肿瘤热疗无选择性的难题具有重要的科学意义。