Erythrocyte-cancer Hybrid Membrane-camouflaged Mesoporous Silica Nanoparticles Loaded with Gboxin for Glioma-targeting Therapy

Objective: The purpose of this research is to formulate a biomimetic drug delivery system, which can selectively target glioblastoma (GBM) to deliver the antitumor agent, Gboxin, a novel Complex V inhibitor. Gboxin can specifically inhibit GBM cell growth but not normal cells.

Methods: In the present study, we utilized red blood cell (RBC) membrane and U251 cell membrane to obtain a hybrid biomimetic membrane (RBC-U), and prepared RBC-U coated Gboxin-loaded mesoporous silica nanoparticles ((MSNs/Gboxin)@[RBC-U]) for GBM chemotherapy. The zeta potential, particle size, and morphology of (MSNs/Gboxin)@[RBC-U] were characterized. The cellular uptake, effect of cells growth inhibition, biocompatibility, and specific self-recognition of nanoparticles were evaluated.

Results: The (MSNs/Gboxin)@[RBC-U] was successfully fabricated and possessed high stability in the circulation system. The drug loading of Gboxin was 13.9%. (MSNs/Gboxin)@ [RBC-U] could effectively retain drugs in the physiological environment and released Gboxin rapidly in the tumor cells. Compared to the MSNs/Gboxin, the (MSNs/Gboxin)@[RBC-U] exhibit highly specific self-recognition to the source cell line. Additionally, the (MSNs/Gboxin) @[RBC-U] showed excellent anti-proliferation efficiency (IC50 = 0.21 μg/mL) in the tumor cell model and few side effects in normal cels in vitro.

Conclusion: The (MSNs/Gboxin)@[RBC-U] exhibited significant anti-cancer effects in vitro and the specific self-recognition to GBM cells. Hence, (MSNs/Gboxin)@[RBC-U] could be a promising delivery system for GBM targeted therapy.

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S8828 Gboxin Gboxin is an inhibitor of oxidative phosphorylation in cancer cells. Gboxin inhibits the activity of F0F1 ATP synthase. It specifically inhibits the growth of primary mouse and human glioblastoma cells but not that of mouse embryonic fibroblasts or neonatal astrocytes.

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