Tumor cell membrane-camouflaged nanoparticles co-delivering docetaxel and metformin for enhanced synergistic therapy of HER2-positive breast cancer.

The clinical efficacy of docetaxel (DTX) in treating HER2-positive breast cancer is hampered by poor solubility and systemic toxicity, while metformin (Met) shows anti-cancer potential by targeting tumor metabolism. We hypothesized that a biomimetic nanoplatform co-delivering DTX and Met could achieve synergistic anti-tumor effects with enhanced safety. This study developed tumor cell membrane-camouflaged mesoporous silica nanoparticles co-loaded with DTX and Met (mem(DTX&Met@MSNs)). The nanoparticles were characterized for particle size, stability, drug loading, and membrane coating. In vitro assays were conducted to assess cellular uptake, cytotoxicity, and synergistic effects. In vivo studies were performed in HER2-positive breast cancer-bearing mice to evaluate biodistribution, anti-tumor efficacy, toxicity, and histopathology. The mem(DTX&Met@MSNs) nanoparticles showed a core-shell structure and pH-responsive release, with over 80% drug release at pH 6.5 versus less than 40% at pH 7.4. Biomimetic coating enabled homologous targeting, enhancing cellular uptake and synergistic cytotoxicity in SK-BR-3 cells (7.89% apoptosis). In vivo, the system prolonged the circulation half-life to nearly 6 h, effectively suppressed tumor growth, and demonstrated excellent biocompatibility with no significant toxicity or body weight loss. In conclusion, mem(DTX&Met@MSNs) integrates homologous targeting with dual-drug synergism, offering a safe and effective strategy for the treatment of HER2-positive breast cancer.