Engineering a Multifunctional Core–Shell Structured Cascade Nanoreactor for Augmented and Synergistic Carbon Monoxide Oncotherapy
Carbon monoxide (CO) therapy has emerged as a promising approach in cancer treatment. Selecting suitable nanocarriers for delivering manganese carbonyl (MnCO), a CO donor, while simultaneously regulating CO release and compensating for hydrogen peroxide (H2O2) and acidity in the tumor microenvironment is crucial for enhancing the effectiveness of CO therapy. In this study, a tumor microenvironment-responsive core-shell structured cascade nanoreactor was designed and synthesized using mesoporous polydopamine (MPDA) as a nanocarrier, followed by loading of MnCO and glucose oxidase-encapsulated zeolite imidazolate framework-8 (GOx@ZIF-8) nanoparticles. Upon entering cancer cells, the protective shell of GOx@ZIF-8 degrades in response to the acidic tumor environment, releasing GOx. GOx catalyzes the conversion of endogenous glucose into gluconic acid and H2O2, accelerating energy starvation in tumor cells. This process, in turn, promotes the reaction between MnCO and H2O2, resulting in in-situ amplified release of CO. Additionally, the excellent photothermal properties of MPDA enable photothermal therapy. This comprehensive antitumor strategy represents a promising advancement in the field of CO-based cancer therapy.