Squid tentacle-mimetic magnetically targeted nanomotors to overcome the bladder barrier for synergistic chemotherapy-immunotherapy of bladder cancer.

Current clinical management of bladder cancer relies on transurethral resection followed by intravesical instillation of therapeutics like Bacillus Calmette-Guérin (BCG) or chemotherapy. However, therapeutic efficacy is significantly hampered by the frequent urination that rapidly clears drugs and the protective glycosaminoglycan (GAG) layer of the urothelium that impedes drug penetration. Furthermore, conventional chemotherapeutics lack tumor specificity, causing collateral damage to normal tissue and compromising bladder function. To address these limitations, we developed a biomimetic nanomotor (MMn/THP/FPEI) inspired by the squid's precision and predatory efficiency. This system consists of magnetic nanoclusters coated with MnO₂ nanosheets, loaded with the chemotherapeutic pirarubicin (THP), and capped with fluorinated polyethyleneimine (FPEI). Under magnetic guidance, the nanomotor navigates the bladder microenvironment like a squid, penetrating the GAG barrier to accumulate selectively at tumor sites. The FPEI layer acts like tentacles, adhering robustly to cancer cells for localized drug retention. Simultaneously, the MnO₂ shell catalytically degrades elevated hydrogen peroxide (H₂O₂) and glutathione (GSH) levels in the tumor microenvironment. This reaction triggers the controlled release of THP and generates immunostimulatory agents (FPEI and Mn2+), synergistically enhancing antitumor immunity. By emulating the squid's hunting strategy, this platform presents a novel paradigm for precise bladder cancer therapy and immunotherapy.