Various physiological characteristics of the tumor microenvironment (TME), such as
hypoxia, overexpression of
glutathione (GSH) and
hydrogen peroxide (H2O2), and mild acidity, can severely reduce the efficacy of many
cancer therapies. Altering the redox balance of the TME and increasing oxidative stress can accordingly enhance the efficacy of
tumor therapy. Herein, we developed a
bismuth-based Cu2+-doped BiOCl nanotherapeutic platform, BCHN, able to self-supply H2O2 for TME-regulated chemodynamic
therapy (CDT) combined with sensitized
radiotherapy (RT). BCHN released H2O2 and consumed GSH to degrade the composite in the slightly acidic TME, and generated
hydroxyl radicals (•OH) via a Fenton-like reaction catalyzed by
copper ions, to achieve oxidative stress-enhanced CDT. The Fenton-like reaction also catalyzed H2O2 to produce O2 to relieve tumor hypoxia, and combined with the X-ray-blocking property of
bismuth to realize TME-enhanced
radiotherapy. Synergistic CDT/RT has previously been shown to effectively inhibit
tumor cell proliferation and achieve effective
tumor control. The current results demonstrated a highly efficient multifunctional bio-degradable nanoplatform for oncotherapy. STATEMENT OF SIGNIFICANCE: Tumor microenvironment-modulated synergy of
radiotherapy and chemodynamic
therapy is conducive to rapid
tumor ablation. Based on this principle, we fabricated a biodegradable BiOCl-based nanocomposite, BCHN. By supplying H2O2, a Fenton-like reaction generated •OH and O2 catalyzed by
copper ions, and consumed
glutathione to biodegrade the composite. Overall, these actions increased
tumor oxidative stress and realized the synergistic anti-
tumor actions of chemodynamic
therapy combined with
bismuth-based sensitization
radiotherapy. This strategy thus provides a unique approach to oncology
therapy.