Cell membrane-camouflaged DOX-loaded β-glucan nanoparticles for highly efficient cancer immunochemotherapy

Biomimetics plays an important role in cancer treatment since it can prolong the circulation of nanoparticles, enhance their delivery and retention in target tissues, and reduce the systemic toxicity of drugs and their carriers. In this study, we developed a biomimetic nanosystem consisting of chemotherapeutic and immunotherapeutic agents wrapped in cell membranes. Specifically, the anti-tumor drug doxorubicin (DOX) was loaded into a bacterial-derived immunomodulatory agent (low molecular weight curdlan, lCUR), and the lCUR-DOX was further wrapped in the red blood cell membrane for camouflage and prolonged circulation. The successful preparation of the lCUR-DOX@RBC nanosystem was supported by various optical and morphological characterizations. In vitro studies indicated that the nanosystem can escape uptake by macrophages, inhibit the invasion of tumor cells, and reprogram M2 macrophages with an immunosuppressive phenotype into M1 macrophages with an immunopromoting phenotype via the MAPK signaling pathway while promoting the phagocytosis of macrophages. In vivo studies showed that the nanosystem effectively inhibits tumor growth in the A-375 tumor-bearing mouse model. Taken together, the above results support further development of the lCUR-DOX@RBC platform for cancer immunochemotherapy in clinical applications.