Department of Oncology, The Second Hospital of Dalian Medical University, Dalian, 116000, People's Republic of China.
Department of Pharmacy, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121000, People's Republic of China.
Sci Rep. 2024 Nov 26;14(1):29402. doi: 10.1038/s41598-024-80735-1.
Breast cancer is one of the most common gynecological malignancies and poses a severe health risk to women. In recent years, ferroptosis therapy has been considered a promising therapeutic strategy for breast cancer by promoting intracellular reactive oxygen species (ROS) production and lipid peroxidation (LPO) accumulation. However, insufficient intracellular ROS levels and suboptimal drug accumulation within breast cancer lesions hinder the efficacy of ferroptosis as a single oncological treatment modality. In this study, we developed a self-targeting biomineralized apoferritin-based nanovector, encapsulating the ferroptosis inducer dihydroartemisinin (DHA), to create a synergistic antitumor nano-platform (Ca/DHA@AFn) capable of achieving dual-mode calcicoptosis and ferroptosis therapy. The Ca/DHA@AFn nanoparticles exhibited uniform distribution, with an average particle size of approximately 20 nm and a drug loading efficiency of 2.32%. MTT assay results demonstrated that Ca/DHA@AFn significantly decreased the viability of 4T1 cells compared to the controls (DHA, Ca@AFn, and DHA@AFn), indicating enhanced therapeutic efficacy. In vivo experiments in mice revealed that Ca/DHA@AFn nanoparticles, through combined calcicoptosis/ferroptosis induction, exhibited superior synergistic antitumor effects compared to single-modality treatments, significantly extending survival and demonstrating high biocompatibility. This study introduces a novel and safe biomineralized apoferritin-based nano-platform leveraging calcicoptosis/ferroptosis dual therapy, showing strong antitumor efficacy against breast cancer cells and presenting a promising strategy for breast cancer treatment.
乳腺癌是最常见的妇科恶性肿瘤之一，对女性健康构成严重威胁。近年来，铁死亡疗法通过促进细胞内活性氧（ROS）的产生和脂质过氧化（LPO）的积累，被认为是一种有前途的乳腺癌治疗策略。然而，细胞内 ROS 水平不足和乳腺癌病变内药物积累不足，限制了铁死亡作为单一肿瘤治疗方式的疗效。在本研究中，我们开发了一种自靶向生物矿化载脂蛋白基纳米载体，包封铁死亡诱导剂二氢青蒿素（DHA），以创建一种能够实现双模式钙凋亡和铁死亡治疗的协同抗肿瘤纳米平台（Ca/DHA@AFn）。Ca/DHA@AFn 纳米粒子表现出均匀的分布，平均粒径约为 20nm，药物载效率为 2.32%。MTT 试验结果表明，与对照组（DHA、Ca@AFn 和 DHA@AFn）相比，Ca/DHA@AFn 显著降低了 4T1 细胞的活力，表明增强了治疗效果。在小鼠体内实验中，Ca/DHA@AFn 纳米粒子通过联合钙凋亡/铁死亡诱导，与单一模式治疗相比，表现出优越的协同抗肿瘤作用，显著延长了生存时间，并表现出高生物相容性。本研究介绍了一种新型的、安全的基于生物矿化载脂蛋白的纳米平台，利用钙凋亡/铁死亡双重治疗，对乳腺癌细胞表现出强大的抗肿瘤疗效，并为乳腺癌治疗提供了一种有前途的策略。
