Abstract

New strategies that enhance both the targetability of chemotherapy drugs and the synergistic effects of chemotherapy and immunotherapy are urgently needed for efficacious solid tumor therapy. In this study, a novel biomimetic nanoparticle system possessing the properties of tumor targeting and immune synergy was designed to meet these requirements. Mesoporous silica nanoparticles loaded with the chemotherapeutic drug doxorubicin (DOX) were coated with cell membranes modified by glycosylphosphatidylinositol (GPI)-anchored anti-HER2 single chain variable fragment (scFv) and the GPI-anchored co-stimulatory molecule CD80 (to promote solid tumor-targeted chemotherapy and cooperated immunotherapy, respectively). The impact of the nanotherapeutic system on both tumor-targeted chemotherapy and cellular immune response was investigated through in vitro and in vivo experiments. The results show that the novel biomimetic therapeutic system effectively promoted antitumor efficiency in vitro and in vivo. In addition, this therapeutic system further enhanced antitumor capacity by increasing CD8+ T cell activation and cytokine production and reducing myeloid-derived suppressor cell (MDSC) levels in tumors.

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