School of Materials Science and Engineering, Key Laboratory of Advanced Civil Materials of Ministry of Education, Tongji University, Shanghai 201804, People's Republic of China.
School of Materials Science and Engineering, Key Laboratory of Advanced Civil Materials of Ministry of Education, Tongji University, Shanghai 201804, People's Republic of China.
Int J Biol Macromol. 2024 Mar;262(Pt 2):129996. doi: 10.1016/j.ijbiomac.2024.129996. Epub 2024 Feb 10.
The limitations of traditional therapeutic methods such as chemotherapy serious restricted the application in tumor treatment, including poor targeting, toxic side effects and poor precision. It is important to develop non-chemotherapeutic systems to achieve precise and efficient tumor treatment. Therefore, a functional metal-organic framework material (MOF) with porphyrin core and doped with Cu and surface-modified with polydopamine (PDA), namely PCN-224(Cu)@PDA (PCP) was designed and prepared. After loaded into the injectable and self-healable hydrogels by dynamic Schiff base bonding of oxidized sodium alginate (OSA) and carboxymethyl chitosan (CMC), the multifunctional nanocomposite hydrogels were obtained, in which Cu in MOF converts to Cu by reacting with glutathione (GSH) which reduces the tumor antioxidant activity to improve the CDT effect. The Cu/Cu induces Fenton-like reaction in tumor cells to produce a toxic hydroxyl radical (OH). PDA achieves photothermal conversion under NIR light for photothermal therapy (PTT), and porphyrin core as a ligand generates reactive oxygen species (ROS), presenting highly efficient photodynamic therapy (PDT). Injectable self-healing hydrogel as a loading platform can be in situ injected to tumor site to release PCP and endocytosed by tumor cells to achieve precise and synergistic CDT-PDT-PTT therapy.
传统治疗方法（如化疗）的局限性严重限制了其在肿瘤治疗中的应用，包括靶向性差、毒副作用大、精准度低等。因此，开发非化疗系统以实现精确高效的肿瘤治疗非常重要。为此，设计并制备了一种具有卟啉核、掺杂铜和表面修饰聚多巴胺（PDA）的功能化金属有机骨架材料（MOF），即 PCN-224（Cu）@PDA（PCP）。通过氧化海藻酸钠（OSA）和羧甲基壳聚糖（CMC）的动态席夫碱键将其负载到可注射和自修复水凝胶中，得到多功能纳米复合水凝胶，其中 MOF 中的 Cu 通过与谷胱甘肽（GSH）反应转化为 Cu，从而降低肿瘤抗氧化活性，提高 CDT 效应。Cu/Cu 在肿瘤细胞中诱导类芬顿反应产生有毒的羟基自由基（OH）。PDA 在近红外光下实现光热转换进行光热治疗（PTT），而卟啉核作为配体产生活性氧（ROS），呈现出高效的光动力治疗（PDT）。可注射自修复水凝胶作为载药平台可以原位注射到肿瘤部位，释放 PCP 并被肿瘤细胞内吞，实现精确的协同 CDT-PDT-PTT 治疗。
