Self-amplified competitive coordination of MnO${}_2$-doped CeO${}_2$ nanozyme for synchronously activated combination therapy

Tumor-specific combination therapy has shown great promise in cancer theranostics. However, the therapeutic efficacy is usually suppressed because most of the therapeutic systems are not able to synchronously activate their different therapeutic approaches and the local concentration of tumor-associated stimulus is generally insufficient to fully activate the combination therapy process. Herein, a MnO${}_2$-doped CeO${}_2$ nanozyme-based nanomedicine (Ce6@CMNRs) is reported for tumor-specific synchronously activated chemodynamic/photodynamic combination therapy. The tumor-overexpressed H${}_2$O${}_2$ substitutes the Ce6 on Ce6@CMNRs surfaces via competitive coordination and then decomposes into $\bullet$OH under acidic condition, achieving the chemodynamic therapy (CDT). Meanwhile, the substituted Ce6 triggers photodynamic therapy (PDT) under laser irradiation that is suppressed before the substitution occurs. Thus, H${}_2$O${}_2$ can synchronously activate both CDT and PDT of Ce6@CMNRs with a similar level in tumor sites. Moreover, the activated PDT-induced oxygen starvation further triggers the generation of H${}_2$O${}_2$ to continuously replace the residual Ce6 coordinated on the nanorod surface, thereby leading to the full activation of PDT and CDT. Also, the doped MnO${}_2$ enhances the generation of $\bullet$OH and provides high contrast for magnetic resonance imaging (MRI) with the help of glutathione. Therefore, Ce6@CMNRs are promising candidates for MRI-guided CDT/PDT combination therapy with minimized side effects and high efficiency. (© 2022 Wiley‐VCH GmbH)