随着现代医疗水平的提高，人们在恶性肿瘤早期诊断与治疗方面的研究也取得了很大的进步与发展。目前，对于肿瘤治疗中的药物递送、光热治疗以及血管栓塞治疗，均取得长足发展。但是，由于其辅助材料种类繁多、功能各异，加之材料本身存在一些不可避免的问题，也在一定程度上限制了它们的研究与应用。基于此，本研究以液态金属和高分子水凝胶为基础材料，采用不同的合成方法和改进策略，制备了三种不同功能的基于液态金属的水凝胶材料，并尝试将其用于肿瘤治疗中的药物释放、光热治疗与化疗联合治疗、血管栓塞治疗。 本文将液态金属液滴引入温度响应型高分子水凝胶中，制备了一种近红外激光响应的水凝胶材料用作药物载体。实验表明，液态金属液滴可以吸收近红外激光光能并转化为热能，使水凝胶的温度得到提升。同时，温度升高引发水凝胶体积收缩（体积可减少62%），将包载的药物释放出来。二者共同抑制肿瘤细胞活性，起到光热治疗与化疗联合治疗的效果。 随后，本文采用液态金属作为光热转换剂，与传统贵金属纳米材料相比，液态金属液滴尺寸大小可控，分散性好，经超声分散后可保存较长时间，且无明显的团聚现象。本文将液态金属液滴和化疗药物包载于壳聚糖中，制备了一种可注射的微球，用于小鼠肿瘤模型的光热治疗与化疗联合治疗。这种微球的制备过程简单，微球尺寸可控（直径范围为6-80 μm）。实验表明，液态金属液滴在微球中具有良好的光热转换能力，在近红外激光照射下3分钟即可升温至60°C，同时微球中的药物进行释放，对小鼠肿瘤的生长表现出明显的抑制作用。 最后，本文制备了一种新型的液态金属/海藻酸钙水凝胶栓塞材料，用于血管栓塞和肿瘤的血管栓塞治疗。由于液态金属液滴的加入，使得该栓塞材料可以在X光和CT下显影，有助于材料使用过程中的定位和监测。该栓塞材料可以在靶血管中实现原位快速固化，阻断血流。实验表明，该栓塞材料材料在动物血管内显影清晰，且用于兔耳耳廓肿瘤模型的血管栓塞治疗效果良好。此外，本文中还对栓塞材料的生物安全性以及血管栓塞的效果进行了多方面的表征（红外热成像、组织切片、数字减影血管造影、磁共振成像等）。 综上，本文以液态金属为主要材料，结合不同功能的高分子水凝胶，制备了三种基于液态金属的水凝胶材料，用于辅助进行不同方式的肿瘤治疗。
With the advancement of modern society and development of medicine, great progress has been made in the research of early diagnosis and therapy of tumors. Now, promising results have been achieved in the field of drug delivery, photothermal therapy and embolotherapy. However, many biomaterials are limited in scientific research and clinic applications because of their various types and functions, as well as the inevitable problems and defects thus involved. Based on this, we prepared three functional liquid metal-loaded polymeric hydrogels through different synthesis and improvement methods. And they were used to drug release, chemophotothermal therapy, and embolotherapy, respectively. The obtained biomaterials have shown good antitumor effect in experiments. For drug release, the near-infrared laser responsive liquid metal-loaded polymeric hydrogels have been prepared as a drug carrier by introducing liquid metal droplets into the temperature responsive hydrogels. The experimental results show that liquid metal can generate heat under near-infrared laser irradiation and make the temperature of hydrogels be improved significantly. Meanwhile, the hydrogels become shrunk (volume decreased by 62%) and release drugs with the increase of temperature. Increased temperature and released drugs by these hydrogles can inhibit the activities of cancer cells. So, the liquid metal-loaded polymeric hydrogels are “smart” carriers for anticancer drug delivery and chemophotothermal therapy. For photothermal therapy, the liquid metal is adopted as photothermal conversion agent in this study. The size of liquid metal droplets is controllable and adjustable compared with traditional noble metal nanomaterials, as well as the dispersion of these droplets is good. After ultrasonic dispersion, the liquid metal droplet solution can be preserved for a long time without obvious agglomeration. Therefore, liquid metal droplets and anticancer drugs are encapsulated in chitosan to prepare injectable microspheres with adjustable size, which can be used in cancer chemophotothermal synergistic therapy. Moreover, the size (diameter range is 6-80 μm) of these microspheres is adjusted by tuning stirring rates, and the preparation process is simple. It has been proven by experiments that the microspheres exhibit excellent photothermal effect, and they are able to raise the local temperature of tumors to 60°C in 3 min under near-infrared laser irradiation. Combined with the release of drugs, the microspheres show better antitumor efficiency in vivo. As the first trial, an injectable and radiopaque liquid metal/calcium alginate hydrogel is introduced and fabricated as an embolic materials candidate for endovascular embolization and tumor embolotherapy through developing liquid metal droplets as radiopaque units into cross-linked networks of biocompatible calcium alginate hydrogels. The adoption of liquid metal droplets makes hydrogels radiopaque under X-ray and CT scan, which facilitates the tracking of embolic materials during surgical vascular operation. In vivo experiments demonstrate that such hydrogels can be performed in blood vessels quickly, and occlude arteries and block flow until they ultimately lead to ischemic necrosis of tumors. In addition, in order to ensure the feasibility and effectiveness of these embolic materials for embolization, the biosafety of these hydrogels and the effect of vascular embolization are characterized in many ways such as infrared thermograph, histological photomicrograph, digital subtraction angiography, and magnetic resonance imaging. Overall, a series of liquid metal-loaded polymeric hydrogels are prepared with liquid metal as the main material combined with different polymers. And they are used as assistant materials for antitumor therapy and show great potentiality in the coming clinics.
