MnO₂ Motor: A Prospective Cancer-Starving Therapy Promoter

Abstract

Here, a tumor-targeted MnO₂ motor nanosystem (designed as MG/HA) was constructed by the assembly of glucose oxidase (GOD), manganese dioxide (MnO₂), and glycoprotein CD44-targeting polymer hyaluronic acid (HA) to elevate cancer-starving therapy efficacy in solid tumor. Upon the specific uptake of MG/HA by CD44 overexpressed cancer cells, GOD catalyzed the oxidation of glucose into gluconic acid and hydrogen peroxide (H₂O₂) accompanying the consumption of oxygen (O₂). Meanwhile, MnO₂ would react with H₂O₂ and acid to generate O₂, which is in turn supplied to the glucose-depletion process, running like a loop. As a result, MnO₂ is displayed as a motor to promote the rate of glucose depletion that contributed to the starving therapy. In contrast to G/HA, MG/HA could not only achieve effective glucose consumption to depress cancer progression, but also alleviate hypoxia and reduce the expression of Glut1 to inhibit the metabolism for further restraining the tumor aggressiveness and metastasis. The concept of MnO₂ motor shows a promising prospect to overcome the restriction of the starving therapy.