Experimental study on novel pH-responsive manganese-based nanoprobes for ferroptosis and magnetic resonance imaging in breast cancer
10.3969/j.issn.1674-8115.2025.09.010
- VernacularTitle:新型pH响应性锰基纳米探针用于乳腺癌铁死亡及磁共振成像实验研究
- Author:
Jingyi WANG
1
;
Jiali DENG
;
Yi ZHU
;
Xinyi DING
;
Jiajing GUO
;
Zhongling WANG
Author Information
1. 上海理工大学健康科学与工程学院,上海 200093;上海交通大学医学院附属第一人民医院放射科,上海 200080
- Publication Type:Journal Article
- Keywords:
breast cancer;
magnetic resonance imaging;
ferroptosis;
combination therapy
- From:
Journal of Shanghai Jiaotong University(Medical Science)
2025;45(9):1183-1193
- CountryChina
- Language:Chinese
-
Abstract:
Objective·To construct a pH-responsive manganese-based nanoprobe and explore the therapeutic efficacy of chemotherapy/ferroptosis synergistic treatment in breast cancer and the effect of pH-responsive magnetic resonance-activated imaging.Methods·BSA-MnO2@CPT(BMC)nanoprobes were prepared by biomineralization,and their physicochemical properties were characterized by transmission electron microscope(TEM)and dynamic light scattering.The magnetic resonance imaging(MRI)was used to evaluate the pH-responsive MRI T1 activation and time-dependent activation efficacy at the cellular level,with quantitative analysis of MRI T1 signal intensity.The reactive oxygen species(ROS)generation and glutathione(GSH)depletion by BMC nanoprobes were respectively detected by methylene blue(MB)and DTNB in vitro.The synergistic efficacy of chemotherapy and ferroptosis mediated by the nanoprobes in 4T1 breast cancer cells was evaluated using the Thiazolyl Blue Tetrazolium Bromide(MTT)assay.After co-incubation 4T1 cells with BMC,intracellular ROS levels were determined through the staining of ROS fluorescence indicator 2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)and the level of lipid peroxide(LPO)expression was detected by using BODIPY581/591 C11 probe.A subcutaneous xenograft tumor model of 4T1 breast cancer was established in mice,with four experimental groups:Control group(PBS group),CPT group,BSA-MnO2(BM)group,and BMC group.The pH-responsive T1 activation effect of the BMC nanoprobes was dynamically monitored in vivo,while the ferroptosis-based antitumor efficacy was evaluated by measuring tumor volume and ferroptosis biomarkers(LPO and ROS).Results·TEM revealed that the prepared BMC nanoprobes exhibited a spherical morphology with an average diameter of approximately 150 nm.The MRI results demonstrated that the nanoprobes were pH-activable,exhibiting progressively enhanced T1 signal intensity under acidic conditions,and displaying pH-dependent r1 relaxivity enhancement.These findings validated their dual pH/time-responsive activation efficacy at the cellular level.In vitro solution-level MB and DTNB assays demonstrated that the BMC nanoprobes effectively enhanced the generation of ROS and the consumption of GSH.Fluorescence staining with DCFH-DA and BODIPY581/591 C11 demonstrated that the combination of ferroptosis effect and chemotherapy significantly enhanced intracellular generation of ROS and LPO accumulation.The MTT assay demonstrated that the survival rate of tumor cells significantly decreased to 17%(P=0.003).In vivo MRI demonstrated that the T1 signal was significantly enhanced and reached its peak at 4 h after tail vein injection of the BMC nanoprobes.Furthermore,in vivo antitumor therapy showed that the BMC group exhibited upregulated levels of LPO and ROS in tumor tissues,accompanied by marked tumor suppression(P=0.009).Conclusion·The pH-responsive theranostic BMC nanoprobes enhances antitumor efficacy via the synergistic interaction of chemotherapy and ferroptosis,while enabling tumor microenvironment-activated MRI.
