Zhang Minyi, Wang Qi, Li Chen, Chen Mengyao, Wang Chunhui, Wang Zikang, Xia Tao, Yi Chengqing, Shi Shuo
School of Chemical Science and Engineering, Department of Clinical Laboratory, Shanghai Tenth People's Hospital, Tongji University, Shanghai 200092, PR China.
Department of Orthopedics, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Huinan Town, Pudong, Shanghai, PR China.
J Adv Res. 2025 Jun 13. doi: 10.1016/j.jare.2025.06.022.
Ion interference therapy has emerged as a promising new treatment for Osteosarcoma (OS). However, its efficacy is significantly restricted by inadequate hydrogen peroxide (HO) under the complex tumor microenvironment (TME).
This study aimed to supply sufficient HO to enhance tumor therapy efficacy and address the limitations associated with ion interference.
A hollow manganese dioxide (HMnO) nanoplatform loaded with calcium peroxide (CaO) (denoted as HMnO@CaO) was evaluated for biosafety through hemolysis tests. The functionality of HMnO@CaO was further validated by quantitative real-time polymerase chain reaction (qRT-PCR) and cytometric analysis.
Excessive Ca accumulation induces endoplasmic reticulum (ER) stress, enhances oxidative stress, and causes mitochondrial damage. Notably, Mn facilitates treatment monitoring through magnetic resonance imaging (MRI). Additionally, Mn-induced ferroptosis triggers an immune response that promotes the polarization of tumor-associated macrophages (TAMs), transforming the pro-tumoral M2 phenotype into the tumoricidal M1 phenotype, thereby enhancing the efficacy of immunotherapy.
In conclusion, HMnO@CaO nanoplatform enhances tumor therapy efficacy by overcoming ferroptosis limitations, inducing Ca overload, and boosting anti-tumor immunity. This strategy offers a promising approach to ion interference in the clinical translation of nanomedicines. Furthermore, it marks a significant advancement in osteosarcoma (OS) treatment and underscores the transformative potential of nanotechnology in medicine.
离子干扰疗法已成为骨肉瘤（OS）一种有前景的新治疗方法。然而，在复杂的肿瘤微环境（TME）中，过氧化氢（HO）不足显著限制了其疗效。
本研究旨在提供充足的HO以提高肿瘤治疗效果，并解决与离子干扰相关的局限性。
通过溶血试验评估负载过氧化钙（CaO）的中空二氧化锰（HMnO）纳米平台（表示为HMnO@CaO）的生物安全性。通过定量实时聚合酶链反应（qRT-PCR）和细胞分析进一步验证HMnO@CaO的功能。
过量的钙积累会诱导内质网（ER）应激，增强氧化应激，并导致线粒体损伤。值得注意的是，锰有助于通过磁共振成像（MRI）进行治疗监测。此外，锰诱导的铁死亡触发免疫反应，促进肿瘤相关巨噬细胞（TAM）的极化，将促肿瘤的M2表型转化为杀肿瘤的M1表型，从而提高免疫治疗的效果。
总之，HMnO@CaO纳米平台通过克服铁死亡局限性、诱导钙超载和增强抗肿瘤免疫力来提高肿瘤治疗效果。该策略为纳米药物临床转化中的离子干扰提供了一种有前景的方法。此外，它标志着骨肉瘤（OS）治疗的重大进展，并强调了纳米技术在医学中的变革潜力。
