分析化学2025，Vol.53Issue(3)：429-440,中插1-中插2,14.DOI:10.19756/j.issn.0253-3820.241452
M1型巨噬细胞衍生纳米囊泡介导三阴性乳腺癌光热-免疫治疗的研究
Photothermal Immunotherapy of Triple Negative Breast Cancer Mediated by M1 Macrophage Derived Nanoparticles
摘要
Abstract
Photothermal therapy,as a novel anti-tumor treatment strategy,faces many challenges such as insufficient targeting,limited penetration ability,and inability to achieve long-term inhibition when used alone for anti-tumor treatment.Based on this,in this study,macrophage extracellular vesicles(MEVs)were modified onto the surface of a vector carrying CSF1R-siRNA and photothermal agents to form a multifunctional gene delivery vector MEVs@RNPs.It could induce the macrophages to reprogram from M2 type to M1 type,so as to achieve efficient photothermal and immunotherapy for triple negative breast cancer(TNBC).The basic physicochemical properties of each nanocarrier were characterized using nanoparticle size analyzer,UV-vis spectrometer,fluorescence spectrometer,thermal imaging instrument,etc.TNBC cells 4T1,endothelial cells Bend3,and macrophages 264.7 were used as in vitro experimental subjects for measurement of MEVs@RNPs.The ability to target tumor cells,kill tumor cells,and induce macrophage reprogramming in vitro was investigated.With Balb/c mice as the in vivo research object,a subcutaneous transplant tumor model was established in mice,and the changes in tumor volume and body weight of mice in different treatment groups were measured.In addition,further isolation of mouse blood and tumor tissue was performed,and hematoxylin-eosin(HE)staining,terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)method,and enzyme-linked immunosorbent assay(ELISA)method were used to determine the apoptosis and cytokine secretion of tumor cells for comprehensive evaluation of MEVs@RNPs.The results showed that the MEVs@RNPs could preferentially target tumor cells and induce stronger TNBC cell killing effect under photothermal conditions.Meanwhile,the results of flow cytometry and ELISA analysis showed that the MEVs@RNPs could promote the transformation of macrophages from M2 type to anti-tumor M1 type,significantly enhancing the secretion levels of anti-tumor cytokines tumor necrosis factor-α(TNF-α)and interleukin-12(IL-12).The in vivo anti-tumor treatment effect assessment of the MEVs@RNPs showed that under laser processing conditions,the MEVs@RNPs could significantly induce pathological necrosis and apoptosis of tumor cells,promote macrophage reprogramming and infiltration of CD4+/CD8+T cells into the tumor site,and enhance the secretion levels of TNF-α and IL-12,thereby comprehensively improving the therapeutic effect of TNBC.关键词
光热治疗/免疫治疗/外泌体/巨噬细胞/重编程/三阴性乳腺癌Key words
Photothermal therapy/Immunotherapy/Exosomes/Macrophage/Reprogramming/Triple negative breast cancer引用本文复制引用
郭彦敏,刘杰,李玮,王鸿玲..M1型巨噬细胞衍生纳米囊泡介导三阴性乳腺癌光热-免疫治疗的研究[J].分析化学,2025,53(3):429-440,中插1-中插2,14.基金项目
烟台市科技计划项目(No.2022MSGY074)资助. Supported by the Scientific Plan Project of Science and Technology Bureau of Yantai(No.2022MSGY074). （No.2022MSGY074）
