Reshaping the tumor microenvironment for increasing the distribution of glucose oxidase in tumor and inhibiting metastasis

Abstract

The poor penetration of solid tumors hinders the development of hunger therapy represented by glucose oxidase (GOx). To address this limitation, we have constructed a GOx/Dex@ZIF-TA nanosystem consisting of tannic acid (TA), carrier ZIF-8, encapsulated GOx and dexamethasone (Dex). In this nanosystem, the loaded Dex can not only expand the pores of the nucleus to promote GOx to enter the nucleus, addressing the shortcomings of short life of reactive oxygen species, but also inhibit the production of collagen to reshape the tumor microenvironment and inhibit lung metastasis. In vivo experiments proved that Dex could inhibit the production of collagen, which increased the accumulation and penetration of the tumor tissues and inhibited lung metastasis. In addition, cell experiments showed that Dex could also enlarge the nuclear pores of the nucleus and promote the entry of drugs into the nucleus. More importantly, Dex is a broad anti-inflammatory drug, and the results of this study should be easily transformed to achieve clinical benefits. Together, this work provided a way to address the limitations of hunger distribution in tumor tissues.