摘要
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 effi-ciency hinder its development.In this study,we prepared alendronate(ALD)/K7M2 cell membranes-coated hollow manganese dioxide(HMnO_(2))nanoparticles as a nanocarrier to load Ginsenoside Rh2(Rh2)for Mag-netic Resonance imaging(MRI)-guided immuno-chemodynamic combination osteosarcoma therapy.Subse-quently,the ALD and K7M2 cell membranes were successively modified on the surface of HMnO_(2) and loaded with Rh2.The tumor microenvironment(TME)-activated Rh2@HMnO_(2)-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@HMnO_(2)-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@HMnO_(2)-AM enhanced the secretion of IL-6,IFN-γand TNF-αin serum and inhibited the generation of FOXP3^(+)T cells(Tregs)in tumors.Moreover,the Rh2@HMnO_(2)-AM treatment significant restricted tumor growth in-situ tumor-bearing mice.Therefore,Rh2@HMnO_(2)-AM may serve as an effective and bio-friendly nanoparticle platform combined with immuno-therapy and chemodynamic therapy to provide a novel approach to osteosarcoma therapy.
基金
This work was financially supported by the National Natural Science Foundation of China(31771048,32071350)
Fundamental Research Funds for the Central Universities(2232018A3-07,2232019A3-06)
International Cooperation Fund of the Science and Technology Com-mission of Shanghai Municipality(19440741600).
