一种用于三阴性乳腺癌的磁靶向纳米诊断与治疗平台。
An Magnetic-Targeting Nano-Diagnosis and Treatment Platform for TNBC.
作者信息
Zhang Mengqi, Bao Shengxian, Qiu Guanhua, Liang Jingchen, Wang Qin, Zhu Xiaoqi, Qin Guchun, Liu Junjie, Zhao Chang
机构信息
Department of Interventional Therapy, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People's Republic of China.
Department of Ultrasound and Department of Radiology, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People's Republic of China.
出版信息
Breast Cancer (Dove Med Press). 2023 Feb 3;15:101-119. doi: 10.2147/BCTT.S387793. eCollection 2023.
PURPOSE
In this experiment, we constructed a magnetic targeting nano-diagnosis and treatment platform of doxorubicin (DOX) combined with iron nanoparticles, and explored their application value and mechanism in the treatment of Triple Negative Breast Cancer (TNBC), as well as its new diagnosis and treatment mode in Magnetic Resonance Imaging (MRI).
PATIENTS AND METHODS
Hollow mesoporous nanoparticles (HFON) were synthesized by solvothermal method, and loaded the drug DOX (DOX@HFON) to treat TNBC. The experiments in vivo and in vitro were carried out according to the characteristics of the materials. In vitro experiments, the killing effect of the drug on cells was verified by cell viability CCK8, ROS generation level, LPO evaluation and flow cytometry; the MRI effect and targeted anti-tumor therapy effect were studied by in vivo experiments; then the tumor tissue sections were detected by Ki-67, CD31, ROS, LPO and TUNEL immunofluorescence detection; H&E staining and blood biochemical tests were used to evaluate the biosafety of the materials.
RESULTS
Through a series of characterization tests, it is confirmed that the nano-materials prepared in this experiment have positive drug loading properties. MDA-MB-231 cells had great phagocytic ability to DOX@HFON under Confocal Laser Scanning Microscope (CLSM). Experiments in vitro confirmed that DOX and Fe were released and concentrated in cells, and a large number of ROS production and induction of LPO were detected by DCFH-DA and C11-BODIPY probes in cells. Apoptosis experiments further confirmed that DOX@HFON induced apoptosis, autophagy and ferroptosis. In the vivo experiment, the anti-tumor therapy effect of MAGNET@DOX@HFON group was the most significant, and in MRI also proved that the drug had great tendency and imaging ability in tumor tissue.
CONCLUSION
The new magnetic targeting nano-diagnosis and treatment platform prepared in this experiment is expected to become a new treatment model for TNBC.
目的
本实验构建阿霉素(DOX)与铁纳米颗粒联合的磁靶向纳米诊疗平台,探究其在三阴性乳腺癌(TNBC)治疗中的应用价值及机制,以及在磁共振成像(MRI)中的新型诊疗模式。
患者与方法
采用溶剂热法合成中空介孔纳米颗粒(HFON),并负载药物DOX(DOX@HFON)用于治疗TNBC。根据材料特性进行体内外实验。体外实验通过细胞活力CCK8、ROS生成水平、LPO评估及流式细胞术验证药物对细胞的杀伤作用;体内实验研究MRI效果及靶向抗肿瘤治疗效果;然后通过Ki-67、CD31、ROS、LPO及TUNEL免疫荧光检测对肿瘤组织切片进行检测;采用苏木精-伊红(H&E)染色及血液生化检测评估材料的生物安全性。
结果
通过一系列表征测试,证实本实验制备的纳米材料具有正载药性能。在共聚焦激光扫描显微镜(CLSM)下,MDA-MB-231细胞对DOX@HFON具有较强的吞噬能力。体外实验证实DOX和Fe在细胞中释放并聚集,通过DCFH-DA和C11-BODIPY探针在细胞中检测到大量ROS生成及LPO诱导。凋亡实验进一步证实DOX@HFON诱导细胞凋亡、自噬和铁死亡。体内实验中,MAGNET@DOX@HFON组的抗肿瘤治疗效果最为显著,MRI也证明该药物在肿瘤组织中有较强的趋向性和成像能力。
结论
本实验制备的新型磁靶向纳米诊疗平台有望成为TNBC的新型治疗模式。