Tumor cell membrane-camouflaged responsive nanoparticles enable MRI-guided immuno-chemodynamic therapy of orthotopic osteosarcoma

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. Construction of tumor microenvironment-responsive nanoplatform for MRI-guided immuno-chemodynamic combination osteosarcoma targeted therapy. [Display omitted] •Ginsenoside Rh2 was loaded in Hollow MnO2 NPs for enhancing its bioavailability.•The orthotopic tumor model exhibits a convincing therapeutic effect of nanosystems.•Alendronate/cell membranes enhance osteosarcoma targeting and tumor-homing ability.•Tumor microenvironment-induced NPs degradation can release immune stimulant and Mn2+.•The NPs had excellent immuno-chemodynamic combination osteosarcoma therapy effect.