A multifunctional oxygen-producing MnO2-based nanoplatform for tumor microenvironment-activated imaging and combination therapy in vitro

Abstract

The current trend of cancer therapy has changed from monotherapy to synergistic or combination therapies. Among the treatment strategies, photodynamic therapy (PDT) and starvation therapy are widely employed together. However, the therapeutic effect of these treatments could lead to strong resistance and poor prognosis due to tumor hypoxia. Therefore, a smart nanoplatform (MONs-GOx@MnO₂-Ce6) has been constructed herein by the assembly of glucose oxidase (GOx)-coated mesoporous organosilica nanoparticles (MONs) and MnO₂ nanosheets-chlorin e6 (Ce6), which form a nanosystem. Once MONs-GOx@MnO₂-Ce6 enter tumor cells, it catalyzes the oxidation of glucose using oxygen (O₂) and generates hydrogen peroxide (H₂O₂) and gluconic acid, the former of which may accelerate the decomposition of MnO₂ nanosheets. The released MnO₂ nanosheets would regenerate O₂ in the presence of H₂O₂. In this case, MnO₂ nanosheets serve as (i) a nanocarrier and fluorescence quencher for the photosensitizer Ce6, (ii) a degradable material that is activated by the tumor microenvironment (TME) for fluorescence recovery, and (iii) an O₂-producing carrier that reacts with H₂O₂ for relieving hypoxia in the tumor, which contributes to the combined starvation/photodynamic cancer therapy since these treatment strategies need O₂. MONs-GOx@MnO₂-Ce6 could not only realize cancer cell imaging, but also reduce intracellular glucose uptake and Glut1 expression, inhibiting the metabolism of cancer cells. This strategy shows great potential for clinical applications.