4.6 Article

Graphene Oxide Nanoparticle-Loaded Ginsenoside Rg3 Improves Photodynamic Therapy in Inhibiting Malignant Progression and Stemness of Osteosarcoma

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FRONTIERS MEDIA SA
DOI: 10.3389/fmolb.2021.663089

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osteosarcoma; graphene oxide; photodynamic therapy; ginsenoside Rg3; stemness

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The study utilized graphene oxide nanoparticles loaded with ginsenoside Rg3 and photosensitizer ICG for photodynamic therapy of osteosarcoma, demonstrating that this combination treatment effectively inhibited proliferation, invasion, migration, and stemness of osteosarcoma cells, with NIR laser enhancing the therapeutic effect significantly.
Osteosarcoma serves as a prevalent bone cancer with a high metastasis and common drug resistance, resulting in poor prognosis and high mortality. Photodynamic therapy (PDT) is a patient-specific and non-invasive tumor therapy. Nanoparticles, like graphene oxide have been widely used in drug delivery and PDT. Ginsenoside Rg3 is a principal ginseng component and has presented significant anti-cancer activities. Here, we constructed the nanoparticles using GO linked with photosensitizer (PS) indocyanine green (ICG), folic acid, and polyethylene glycol (PEG), and loaded with Rg3 (PEG-GO-FA/ICG-Rg3). We aimed to explore the effect of PEG-GO-FA/ICG-Rg3 combined with PDT for the treatment of osteosarcoma. Significantly, we found that Rg3 repressed proliferation, invasion, and migration, and enhanced apoptosis and autophagy of osteosarcoma cells, while the PEG-GO-FA/ICG-Rg3 presented a higher activity, in which NIR laser co-treatment could remarkably increase the effect of PEG-GO-FA/ICG-Rg3. Meanwhile, stemness of osteosarcoma cell-derived cancer stem cells was inhibited by Rg3 and PEG-GO-FA/ICG-Rg3, and the combination of PEG-GO-FA/ICG-Rg3 with NIR laser further significantly attenuated this phenotype in the system. Moreover, NIR laser notably improved the inhibitor effect of PEG-GO-FA/ICG-Rg3 on the tumor growth of osteosarcoma cells in vivo. Consequently, we concluded that PEG-GO-FA/ICG-Rg3 improved PDT in inhibiting malignant progression and stemness of osteosarcoma cell. Our finding provides a promising and practical therapeutic strategy for the combined treatment of osteosarcoma.

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