多功能CuS纳米摇铃的构建及其在癌症诊治中的应用研究

Photothermal therapy (PTT) mediated by near-infrared light irradiation has gained popularity as a promising minimally invasive technique for cancer therapy. However, it is difficult to completely eradicate tumor cells by PTT. In addition, due to the lack of functional groups, it is not easy to carry drugs as well as targeting molecules for inorganic PTT agents. In this project we try to develop multifunctional gelatin stabilized CuS nanorattles with superparamagnetic Fe3O4 nanoparticles as their cores and biocompatible gelatin macromolecules as their protectants. Due to the thermo-sensitive and enzyme-sensitive properties of gelatin macromolecules, chemotherapeutic drug is loaded into the hollow CuS nanorattles, realizing tumor magnetic targeting, magnetic resonance imaging for cancer diagnosis, tumor-site specific enzyme and light responsive drug release and combined therapy. The successful development of multifunctional CuS nanorattles PTT agents shows many advantages including overcoming the limitation of single PTT treatment, solving the difficulties of loading drugs into inorganic PTT agents, improving the targeting capability and laying the theoretical and technical foundation for developing novel PTT agents and effective cancer diagnosis and therapy.

近红外光介导的光热治疗是一种新兴的微创肿瘤治疗技术，然而单一的光热治疗无法完全去除肿瘤细胞，并且常用的无机光热治疗剂普遍存在携载药物困难、靶向性差等缺陷。因此，本项目拟制备一种多功能CuS纳米摇铃（Nanorattle）光热治疗剂，其内核为磁性Fe3O4纳米粒子、保护层为生物相容性良好的明胶蛋白,利用明胶蛋白对温度和酶敏感的特性将化疗药物装载到CuS纳米摇铃的空腔中，实现集肿瘤磁靶向、磁共振成像诊断、肿瘤部位光可控型及酶响应型药物释放以及光热治疗与化疗联合作用于一体。该多功能CuS纳米摇铃光热治疗剂的成功研制不仅能克服单一光热治疗的局限性，解决无机光热治疗剂载药困难等问题，同时能够提高癌症治疗的靶向性，为开发新型光热治疗剂及癌症的有效诊断和治疗奠定理论和技术基础。

近红外光介导的光热治疗是一种新兴的微创肿瘤治疗技术，然而单一的光热治疗无法完全去除肿瘤细胞，并且常用的无机光热治疗剂普遍存在携载药物困难、靶向性差，粒径较大而导致在体内无法完全清除等缺陷。因此，在项目执行期间，课题组研发了一系列金属硫族光热治疗剂，其中代表性工作为：1）为了克服纳米粒子在瘤内递送受到瘤体致密及高组织渗透压的阻碍，课题组设计合成了碲化铜、硒化镍及硒化钴超小纳米颗粒，并成功在粒子表面成功装载化疗药物阿霉素，因其较小的颗粒尺寸实现体内易清除及肿瘤部位光热和化疗联合治疗的效果，相关研究成果发表在ACS applied materials & interfaces等期刊上；2）为了克服硒化铜纳米结构的合成过程大多涉及毒性较大的原材料及高温环境等缺陷，课题组开发一种低温，环境友好的新型合成策略得到形貌、晶型可控的硒化铜纳米结构，并表征了其在光催化及光热杀伤肿瘤的应用前景，相关研究成果发表在Nanoscale期刊上。在本项目（项目号为81501590）资助下，以通讯作者身份发表标注基金项目号的SCI论文9篇，申请专利6项（已实审5项）。项目执行期间，曾三次被行业内国际会议邀请做分会场邀请报告，取得了较好的学术交流效果。综上所述，项目主持人在项目组成员的合作下，较好的完成了本项目的预期目标。