光热协同铁死亡疗法的二氧化锰纳米材料用于抗口腔鳞状细胞癌研究  

Manganese dioxide nanomaterials for photothermal synergistic ferroptosis therapy against oral squamous cell carcinoma

作　　者：李矗 杨宏宇 Li Chu;Yang Hongyu(School of Stomatology,Zunyi Medical University,Zunyi Guizhou 563006,China;Department of Oral and Maxillofacial Surgery,Stomatological Center,Peking University Shenzhen Hospital,Shenzhen Guangdong 518036,China)

机构地区：[1]遵义医科大学口腔医学院,贵州遵义563006 [2]北京大学深圳医院口腔医学中心口腔颌面外科,广东深圳518036

出　　处：《遵义医科大学学报》2025年第3期227-233,共7页Journal of Zunyi Medical University

基　　金：深圳市科技创新委员会基础研究重点项目(NO:JCYJ20220818102816036)。

摘　　要：目的 以具有光热性质的二氧化锰纳米粒子为核,单宁酸与铁配位为壳,载入铁死亡药物RSL3,构建纳米载药平台,探究光热联合铁死亡疗法抗口腔鳞状细胞癌(OSCC)的效果。方法 采用模板法合成中空介孔二氧化锰并负载铁死亡诱导剂RSL3,单宁酸与铁在表面配位修饰。对合成的纳米材料进行表征,确定其结构。然后,评价纳米颗粒的光热性能及模拟肿瘤微环境的药物释放。最后,将纳米材料作用于OSCC细胞,进行体外细胞实验。结果 在近红外光辐照及模拟肿瘤微环境的条件下,RSL3在1 h内释放量达到(40.13±3.8)%,明显高于无近红外光辐照的释放量(19.78±3.2)%,t=58.75,P=0.000 3;在模拟肿瘤微环境的体外实验中,35μg/mL的纳米材料作用于肿瘤细胞并实施近红外光辐照后,其HSC3和HN6细胞存活率分别为(4.5±0.72)%及(4.8±0.76)%;Western blot检测结果进一步验证了纳米材料介导的铁死亡作用。结论 成功构建二氧化锰纳米材料,光热实验、药物释放实验以及细胞实验表明该纳米材料具有良好的抗肿瘤效果。Objective A nanoplatform was constructed using the photothermal-responsive manganese dioxide(MnO 2)nanoparticles as the core and tannic acid coordinated with iron(TA/Fe 3+)as the shell.The ferroptosis drug(RSL3)was loaded into the nanoplatform to explore the effect of photothermal combined with ferroptosis therapy on oral squamous cell carcinoma(OSCC).Methods The hollow mesoporous MnO 2 nanoparticles were synthesized using a template method and loaded with ferroptosis inducer RSL3,which were further coated with TA/Fe 3+for modification.The synthesized MnO 2 nanoplatform was characterized by SEM and TEM,and the photothermal performance and drug release in the tumor microenvironment were also evaluated.Finally,the MnO 2 nanoplatform was applied to OSCC cells for in vitro experiments.Results Under the conditions of near-infrared(NIR)light irradiation and simulated tumor microenvironment,the release of RSL3 reached to(40.13±3.8)%within 1 hour,significantly higher than that without NIR light irradiation(19.78±3.2)%,t=58.75,P=0.0003.When the OSCC cells were treated with 35μg/ml of MnO 2 nanoplatform and subjected to NIR light irradiation,the survival rate of HSC3 and HN6 cells was(4.5±0.72)%and(4.8±0.76)%,respectively.Western blot assay results further validated the nanomaterial-mediated ferroptosis effect.Conclusion The MnO 2 nanoplatform was successfully constructed and showed excellent photothermal performance and controlled drug release behaviors.The cell experiments revealed that the OSCC cells were efficiently killed through the combined photothermal therapy and ferroptosis therapy.

关 键 词：口腔鳞状细胞癌 光热疗法 铁死亡 二氧化锰纳米材料 

分 类 号：R739.86[医药卫生—肿瘤]