癌症诊治用普鲁士蓝纳米制剂的设计制备与性能评价

发布时间：2018-04-25 15:25

本文选题：纳米普鲁士蓝 + 医学成像　；参考：《哈尔滨工业大学》2016年博士论文

【摘要】：癌症早期诊断与根治是医学上的重要课题,新兴的纳米技术为癌症诊治提供了新思路,多种纳米材料具备特殊理化性质,可实现癌症高效诊断与治疗。普鲁士蓝是一类由Fe2+与Fe3+形成的亚铁氰化铁,是美国FDA批准的治疗铊和铯等重金属中毒的口服药物。已有研究表明普鲁士蓝纳米材料具有光热转换性能,可作为一种高效光热治疗剂用于癌症光热治疗。基于普鲁士蓝纳米材料的光热治疗功能,本研究设计制备了一系列具有癌症诊治功能的普鲁士蓝纳米制剂。将透明质酸-聚乙二醇共聚物修饰于普鲁士蓝纳米粒子表面制备得到具有癌靶向和光热治疗特性的普鲁士蓝纳米粒子。粒子通过透明质酸与癌细胞表面细胞粘附分子CD44之间的特异性结合实现癌症主动靶向。与普通普鲁士蓝纳米粒子相比,靶向普鲁士蓝纳米粒子在癌细胞中摄取率显著提高。体外研究表明靶向普鲁士蓝纳米粒子具有更为优越的光热治疗效果。在此基础上,进一步制备了透明质酸-聚乙二醇共聚物修饰的载药介孔普鲁士蓝纳米粒子,实现了癌靶向和光热/药物协同治疗。体外细胞实验和荷瘤裸鼠模型治疗结果显示,与单独的靶向光热治疗和靶向药物治疗相比,靶向载药介孔普鲁士蓝纳米粒子装载抗癌药物10-羟基喜树碱后显著增强了疗效。普鲁士蓝纳米材料在波长范围为650-1100 nm的近红外区域具有强吸收特性,本研究首次发现普鲁士蓝纳米粒子可在765 nm近红外脉冲激光照射下产生光声信号,光声成像组织穿透深度可达4.3 cm。小鼠头部光声成像实验表明普鲁士蓝纳米粒子能显著提高小鼠脑部血管和脑实质光声图像对比度,且其成像能力更为持久。基于金纳米粒子的CT成像性能和普鲁士蓝纳米粒子的光声成像和光热治疗性能,本研究设计制备了金/普鲁士蓝纳米粒子,是一种具有普鲁士蓝壳层结构的金纳米粒子。荷瘤裸鼠实验表明,金/普鲁士蓝纳米粒子可使光声成像与CT成像有效结合,能准确诊断和定位,并实现在近红外激光照射下的实时癌症光热治疗。本研究在前期研究基础上进一步发展创新,实现了基于普鲁士蓝纳米材料的癌症靶向光热治疗和癌症靶向光热/药物联合治疗。此外,本研究首次发现普鲁士蓝纳米粒子的光声成像特性并将其应用于双模态成像介导的癌症光热治疗。研究进一步拓展和提升了普鲁士蓝纳米材料在癌症诊断和治疗中的功能,具有一定创新意义和应用前景。
[Abstract]:Early diagnosis and radical cure of cancer is an important subject in medicine. The new nanotechnology provides a new idea for cancer diagnosis and treatment. Many nanomaterials have special physical and chemical properties and can be used to diagnose and treat cancer efficiently. Prussian blue is a kind of ferric cyanide formed by Fe2 and Fe3. It is an oral drug approved by FDA to treat heavy metal poisoning such as thallium and cesium. Studies have shown that Prussian blue nanomaterials have photothermal conversion properties and can be used as an effective photothermal therapy agent for cancer photothermal therapy. Based on the photothermal therapy of Prussian blue nanomaterials, a series of Prussian blue nanopharmaceuticals with cancer diagnosis and treatment were designed and prepared. Prussian blue nanoparticles were prepared by modifying hyaluronic acid-polyethylene glycol copolymer onto the surface of Prussian blue nanoparticles. The particles achieve the active targeting of cancer by the specific binding of hyaluronic acid to the cell adhesion molecule CD44 on the cancer cell surface. Compared with ordinary Prussian blue nanoparticles, the uptake rate of targeted Prussian blue nanoparticles in cancer cells was significantly increased. In vitro studies show that targeted Prussian blue nanoparticles have better photothermal effects. On this basis, the mesoporous Prussian blue nanoparticles modified by hyaluronic acid-polyethylene glycol copolymer were further prepared, and the cancer targeting and photothermal / drug synergistic therapy were achieved. The results of cell experiments in vitro and tumor-bearing nude mice model showed that, compared with the single targeted photothermal therapy and targeted drug therapy, the anti-cancer drug 10-hydroxycamptothecin was significantly enhanced by the immobilized mesoporous blue nanoparticles loaded with 10-hydroxycamptothecin. Prussian blue nanomaterials have strong absorption properties in the near infrared region of 650-1100 nm. It is the first time to find that Prussian blue nanoparticles can produce photoacoustic signals under the irradiation of 765 nm near infrared pulse laser. The penetrating depth of photoacoustic imaging tissue can reach 4.3 cm. The photoacoustic imaging experiment of mouse head showed that Prussian blue nanoparticles could significantly improve the contrast of photoacoustic images of blood vessels and brain parenchyma of mice, and its imaging ability was more lasting. Based on the CT imaging properties of gold nanoparticles and the photoacoustic imaging and photothermal treatment properties of Prussian blue nanoparticles, gold / Prussian blue nanoparticles were designed and prepared, which is a kind of gold nanoparticles with Prussian blue shell structure. Experiments in nude mice show that gold / Prussian blue nanoparticles can effectively combine photoacoustic imaging with CT imaging, can accurately diagnose and locate cancer, and realize real-time photothermal treatment of cancer under near-infrared laser irradiation. On the basis of previous studies, this study further developed and innovated to realize the combination of photothermal therapy and combination therapy based on Prussian blue nanomaterials. In addition, the photoacoustic imaging properties of Prussian blue nanoparticles were first found and applied to bimodal imaging mediated photothermal therapy of cancer. The research has further expanded and improved the function of Prussian blue nanomaterials in cancer diagnosis and treatment.
【学位授予单位】：哈尔滨工业大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R730.5

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