中国肿瘤生物治疗杂志2026，Vol.33Issue(3)：262-269,8.DOI:10.3872/j.issn.1007-385x.2026.03.005
负载DMXAA的锰卟啉金属有机框架纳米协同声动力疗法治疗三阴性乳腺癌小鼠移植瘤
Manganese porphyrin metal-organic framework nanoparticles loaded with DMXAA combined with sonodynamic therapy for the treatment of triple-negative breast cancer mouse xenografts
摘要
Abstract
Objective:To construct manganese porphyrin metal-organic framework nanoparticles(DPM)loaded with the STING agonist DMXAA,and to investigate their therapeutic effect against triple-negative breast cancer(TNBC)cells(4T1)and 4T1 cell-mouse xenografts.Methods:DPM nanoparticles were prepared by physical adsorption.Their morphology and physicochemical properties were characterized using transmission electron microscopy(TEM),scanning electron microscopy(SEM),and a nanoparticle size analyzer.4T1 cells were cultured and divided into the following experimental groups:Control,Ultrasound Irradiation(US),DPM Treatment(DPM),and DPM Treatment combined with Ultrasound Irradiation(DPM+US).Cell viability was assessed using the CCK-8 assay.The expression of high mobility group box 1(HMGB1)and calreticulin(CRT)was detected using immunofluorescence.Expression of STING pathway-related proteins was analyzed using WB.A 4T1 cell xenograft model was constructed and randomly divided into four groups.Following the treatments as those in the cell experiments,tumor volume was measured,and immunofluorescence was used to detect the expression of Ki-67,HMGB1,CRT,and hypoxia inducible factor-1ɑ(HIF-1α)in the transplanted tumor tissues.Additionally,TUNEL assay was used to detect cell apoptosis,flow cytometry was applied to assess immune cell activation,and H-E staining was used to evaluate the safety of the nanoparticles in major organs.Results:DPM exhibited a spindle shape with an average particle size of(268±3.302)nm and a zeta potential of(33.1±0.87)mV.In cell experiments,DPM combined with ultrasound irradiation significantly inhibited 4T1 cell growth(P<0.001),elevated ROS levels(P<0.001),induced upregulation of CRT expression(P<0.001),and caused the translocation of HMGB1 from the nucleus to the cytoplasm.In addition,the STING signaling pathway was activated,as evidenced by significantly increased expression of p-STING,p-TBK1,and p-IRF3 proteins(all P<0.001).In vivo,DPM combined with ultrasound irradiation significantly inhibited the growth of 4T1 cell xenograft(P<0.001),promoted immune cell phenotypic transformation(P<0.001),suppressed Ki-67 and HIF-1α expression in xenograft tissues,and reduced GSH production(P<0.01).It also promoted CRT and HMGB1 protein expression and ROS production(P<0.001).No significant effects on major organ structures were observed.Conclusion:DPM combined with ultrasound irradiation can significantly inhibit the growth of 4T1 cells and the xenografts through activation of the STING pathway,induce antitumor immune responses,and show no obvious toxicity to major organs.关键词
声动力治疗/免疫治疗/金属有机框架/STING激动剂/三阴性乳腺癌Key words
sonodynamic therapy/immunotherapy/metal-organic framework/STING agonist/triple-negative breast cancer(TNBC)分类
医药卫生引用本文复制引用
刘乾辉,桂斌,蒲欢,李周畅,黄鑫,周青,邓倾..负载DMXAA的锰卟啉金属有机框架纳米协同声动力疗法治疗三阴性乳腺癌小鼠移植瘤[J].中国肿瘤生物治疗杂志,2026,33(3):262-269,8.基金项目
国家自然科学基金(81901759,82271999) （81901759,82271999）
武汉大学人民医院交叉创新人才项目(JCRCFZ-2022-004) （JCRCFZ-2022-004）
