Engineering a multifunctional core-shell structured cascade nanoreactor for augmented and synergistic carbon monoxide oncotherapy

Abstract

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.