中空钨酸铋载药纳米粒用于光响应癌症联合治疗的研究

Chemotherapy is one of the main cancer treatment, but low bioavailability and causing serious side effects have greatly affected its cancer treatment effect. Using nano carriers is a promising way to effectively improve the efficacy of chemo drugs. And many recent discovered nano carriers themselves are photo thermal or other treatment agent，which will assist chemo drug to overcome tumor heterogeneity and drug resistance leaded chemotherapy insensitivity. Additionally, nano carriers are easy to be modified by targeted molecules and achieve drug controlled release, and drug targeted delivery and controlled release are valid strategies to reduce toxic side effects. Therefore, this project innovatively utilizes mesoporous hollow structure bismuth tungstate nanoparticles as drug carrier, by means of loading chemo drugs, phase-change materials and tumor cell membrane targeted modification, achieve near-infrared light induced phase change temperature responded drug release, targeted drug delivery and synergistic therapy of photothermal therapy, non-oxygen consume photodynamic therapy and chemotherapy. And the contrast enhancement function of the carrier itself can also realize imaging guided therapy. By exploring and discovering high-targeted low-toxicity temperature-responsive drug loaded nano carriers, this project is expected to provide useful theoretical and practical basis for the development of highly effective tumor treatment methods. This research project has strong theoretical research significance and potential application value.

化疗是癌症治疗的主要手段之一，但化疗药生物利用度低，且会产生毒副作用，严重影响其癌症治疗效果。利用纳米药物载体进行药物运输是提高化疗药药效的有效方法，且近年来新兴的很多纳米载体本身具光热治疗等作用，可协同增效化疗，克服肿瘤异质性及耐药导致化疗不敏感等问题。此外，纳米药物载体易于修饰，且可实现药物控释，药物的靶向递送和控制释放将有效降低药物毒副作用。因此本项目创新性制备具介孔中空结构钨酸铋纳米粒，装载化疗药和相变材料，并用肿瘤细胞膜修饰实现靶向功能。所构建的近红外光诱导相变型温度响应性药物控释、具靶向组合治疗功能的纳米粒，可实现肿瘤的光热、非耗氧光动力及化疗高效协同治疗，载体本身所具备的造影增强功能还可实现成像引导治疗。本项目通过探索和发现高靶向低毒性温度响应性载药纳米粒，有望为开发高效的肿瘤治疗方法提供有益的理论和实践依据，具有较强理论研究意义和潜在应用价值。

近年来，随着纳米技术的发展，多功能纳米药物在肿瘤治疗等生物医学领域的研究日益广泛。在本项目的资助下，我们共完成了五种新型纳米材料的构建并对其在生物医学领域的应用进行了初步的效果评价。我们构建了一种新型的钨酸铋纳米材料，改善了钨酸铋纳米材料在光热治疗方面光热转换效率低的问题并提高了光催化性能；构建了一种基于硫化铋的新型纳米载体，提高了材料的光热转换性能的同时增强了其光催化活性，通过装载相变材料和小檗碱药物，实现了温度响应性控释大幅提高了药物的抗癌活性并降低了其对机体的毒副作用。我们还构建了一种钴掺杂的中空聚多巴胺纳米材料，该材料通过微量钴元素的掺杂实现了催化过氧化氢产生氧气和谷胱甘肽消耗功能，可增敏化疗/光热治疗联合治疗提高肿瘤的治疗效果。此外，我们还构建了一种磁性和近红外双响应聚吡咯包覆Fe3O4纳米颗粒用于细菌去除和灭活，该材料不仅可通过绿色方法制备且可回收重复利用，适用于可持续发展战略指导下的抗菌领域应用。最后我们还构建了一种基于金属多酚网络结构的多功能纳米材料用于抗菌治疗，其较好的生物相容性和较高的抗菌活性提示其具有广泛的应用前景。