Osteosarcoma is a refractory bone disease in young people that needs the updating and development of effective treatment. Although nanotechnology is widely applied in cancer therapy, poor targeting and inadequate efficiency hinder its development. In this study, we prepared alendronate (ALD)/K7M2 cell membranes-coated hollow manganese dioxide (HMnO₂) nanoparticles as a nanocarrier to load Ginsenoside Rh2 (Rh2) for Magnetic Resonance imaging (MRI)-guided immuno-chemodynamic combination osteosarcoma therapy. Subsequently, the ALD and K7M2 cell membranes were successively modified on the surface of HMnO₂ and loaded with Rh2. The tumor microenvironment (TME)-activated Rh2@HMnO₂-AM nanoparticles have good bone tumor-targeting and tumor-homing capabilities, excellent GSH-sensitive drug release profile and MRI capability, and attractive immuno-chemodynamic combined therapeutic efficiency. The Rh2@HMnO₂-AM nanoparticles can effectively trigger immunogenic cell death (ICD), activate CD4⁺/CD8⁺ T cells in vivo, and upregulate BAX, BCL-2 and Caspase-3 in cellular level. Further results revealed that Rh2@HMnO₂-AM enhanced the secretion of IL-6, IFN-γ and TNF-α in serum and inhibited the generation of FOXP3⁺ T cells (Tregs) in tumors. Moreover, the Rh2@HMnO₂-AM treatment significant restricted tumor growth in-situ tumor-bearing mice. Therefore, Rh2@HMnO₂-AM may serve as an effective and bio-friendly nanoparticle platform combined with immunotherapy and chemodynamic therapy to provide a novel approach to osteosarcoma therapy.

骨肉瘤是一种青少年难治性骨病，需要更新和开发有效的治疗方法。虽然纳米技术在癌症治疗中得到了广泛的应用，但靶向性差、效率低下阻碍了其发展。在这项研究中，我们制备了阿仑膦酸盐 (ALD)/K7M2 细胞膜包覆的中空二氧化锰 (HMnO ₂ ) 纳米颗粒作为纳米载体，负载人参皂苷 Rh2 (Rh2) 用于磁共振成像 (MRI) 引导的免疫-化学动力学联合骨肉瘤治疗。随后，ALD和K7M2细胞膜相继在HMnO ₂表面修饰并负载Rh2。肿瘤微环境 (TME) 激活的 Rh2@HMnO ₂-AM纳米粒子具有良好的骨肿瘤靶向和肿瘤归巢能力、优异的GSH敏感药物释放曲线和MRI能力以及具有吸引力的免疫-化学动力学联合治疗效率。Rh2@HMnO ₂ -AM 纳米粒子可有效触发免疫原性细胞死亡 (ICD)，激活体内 CD4 + ^/ CD8 ⁺ T 细胞，并在细胞水平上调 BAX、BCL-2 和 Caspase-3。进一步的结果表明，Rh2@HMnO ₂ -AM 可增强血清中 IL-6、IFN-γ 和 TNF-α 的分泌，并抑制肿瘤中 FOXP3 ⁺ T 细胞 (Tregs) 的生成。此外，Rh2@HMnO ₂ -AM 治疗显着限制了肿瘤的原位生长荷瘤小鼠。因此，Rh2@HMnO ₂ -AM 可以作为一种有效且生物友好的纳米颗粒平台，结合免疫疗法和化学动力学疗法，为骨肉瘤治疗提供一种新方法。