二硫化钼双载药杂化超分子水凝胶的制备及其在肿瘤协同治疗中的研究

Cancer is a disease caused by abnormal control mechanisms of cell growth, which has the characteristics of unlimited proliferation, transformation and metastasis. As a global health problem, it is the one of the leading cause of death worldwide. So far, cancer treatment has always been a problem to be solved in the field of biomedicine. With the development of nanomedicine and nanotechnology, the synergistic therapy strategy based on nanomaterials has become a new trend and has had a profound impact on cancer treatment. . Molybdenum disulfide (MoS2) with different morphology was studied as research object and photothermal absorber in this project. To evaluate the relationship between the structural differences of MoS2 and gel morphology, supramolecular hybrid hydrogels based on MoS2 with different morphology were prepared using the combination of the host-guest interaction between one end of the PEG blocks and α-CD and the hydrophobic aggregation of the MoS2. Meanwhile, utilizing Hydrophobic interaction between MoS2 and hydrophobic drugs, and the high hydrophilic property of gel structure, dual-drug delivery system was realized. Investigating the effect of different morphological structure of MoS2 on the dual drug release behavior, as well as the relationship of synergistic chemotherapy-photothermal therapy of tumor in vitro and in vivo will provide new research ideas and theoretical basises for the development of novel drug carriers.

癌症是一种由控制细胞生长增殖机制失常而引起的疾病，具有无限增殖、可转化和易转移特点，是目前世界上导致人类死亡的主要因素之一。它作为全球性的健康问题，对其进行有效治疗或治愈一直都是有待攻克的重大医学问题。随着纳米医学及纳米技术的发展，基于纳米材料的协同治疗已经成为一种新的趋势，对癌症的治疗有着极其深远的影响。. 本项目拟以不同形貌的二硫化钼（MoS2）无机纳米材料为研究对象和光热吸收剂，利用MoS2疏水聚集作用及聚乙二醇与α-环糊精的主客体识别作用，制备出基于不同形貌MoS2的杂化超分子水凝胶，探索MoS2结构差异对凝胶形貌影响的关系；利用MoS2与疏水药物的疏水作用及凝胶结构的高亲水特性实现不同极性双药物的同时负载，揭示不同形貌结构的MoS2在双药物释放行为以及细胞、活体水平下肿瘤化疗与光热协同治疗方面的差异关系，为开发新型超分子水凝胶药物载体提供新的研究思路和基础依据。

多聚准轮烷（PPR）超分子水凝胶是基于α-环糊精（α-CD）与聚乙二醇（PEG）部分包合形成PPR，之后利用相邻PPR之间强烈的氢键作用形成结晶微区，而未被包合的PEG链仍然保持其亲水性能而实现三维空间网状结构的形成。该类凝胶不仅制备条件温和、生物相容性好，而且具有温度响应的相转变行为和剪切变稀等特点，在药物控释领域显示出巨大的应用前景。但是该凝胶的形成是需要高分子量PEG为原料，这限制它更好地被应用于临床治疗中。本项目以二硫化钼纳米片、低分子量PEG为研究对象，通过α-CD与低分子量PEG的包结络合作用及二硫化钼纳米片额外超分子交联点的引入，制备了功能化新型杂化超分子水凝胶，并研究了其药物控释行为。二硫化钼及环糊精在环境保护、分析检测等方面也有着广泛的应用，我们也对二硫化钼及β-环糊精在水处理及传感器方面进行了相关研究，制备了吸附材料用于污染物的吸附研究；制备了传感器用于生物样品中药物的检测。