Biomimetic immortalized mesenchymal stem cell-based nanoparticles suppress orthotopic postsurgical glioma via CD73 targeting and chemotherapy

Glioma is highly prone to recurrence post-surgery, and effective postoperative adjuvant therapeutic agents are lacking. Developing drugs that can efficiently cross the blood-brain barrier and target postoperative glioma is crucial for overcoming the challenges associated with the treatment of glioma. Nanomaterials modified with cell membranes have shown promise in crossing the blood-brain barrier for the treatment of glioma, but the origin of the cells as well as their heterogeneity are the current bottlenecks of this strategy. Previously, we demonstrated that immortalized mesenchymal stem cell membranes retain natural tumor-homing capability and offer a stable, scalable, and uniform source for sustained tumor targeting. Here, we proposed the use of immortalized mesenchymal stem cell plasma membranes with tumor-homing properties as carriers to develop biomimetic nanoparticles loaded with shCD73 and doxorubicin, named Lipo-PM@shCD73@DOX. By harnessing the tumor-homing factors, the developed biomimetic nanoparticles effectively crossed the blood-brain barrier and targeted postoperative residual glioma tissues to achieve postoperative gene therapy and chemotherapy for glioma. The present study demonstrates the therapeutic efficacy of biomimetic nanoparticles in delaying glioma progression by inhibiting cellular proliferation and inducing apoptosis. Additionally, we confirmed the in vitro and in vivo biosafety of biomimetic nanoparticles. In conclusion, this study overcame the problems of insufficient cell source and cellular heterogeneity in previous mimetic strategies and developed anti-glioma targeting drug biomimetic nanoparticles that efficiently cross the blood-brain barrier. It constitutes a novel anti-glioma adjuvant that enhances postoperative therapy and delays recurrence.