Enhancing catalase-like activity of Prussian blue nanozyme by gadolinium-doping for imaging-guided antitumor amplification via photodynamic therapy and chemotherapy

Deprivation of O2 in most solid tumors greatly limits the effectiveness of photodynamic therapy. Prussian blue nanozyme (PBzyme) are reported to possess catalase-like (CAT) activity to alleviate tumor hypoxia. However, the low catalytic activity is far from satisfactory. Metal doping may improve the catalytic activity of PBzyme, but there are few reports in this regard. Herein, by a screening of metal dopants, Gd-doped PB with enhanced CAT activity is constructed on the basis of small-sized hollow mesoporous silica nanoparticles. Theoretical calculation demonstrates that Gd regulates the state density population of Fe in PBzyme and reduces the Gibbs free energy of CAT catalytic cycle, thus improving its CAT activity (approximately 4 times higher than that of pure PBzyme). After conjugated with photosensitizer Ce6 and tumor-targeted molecule folic acid and loaded with chemotherapy drug doxorubicin, the nanoplatform displays dual-enhanced T1 and T2 imaging capacity simultaneously. Upon high accumulation in tumors, the nanoplatform demonstrates augmented antitumor effects by combining enhanced photodynamic therapy and doxorubicin-mediated chemotherapy both in vitro and in vivo. This work demonstrates that the integration of Gd into PBzyme is an effective strategy to improve the catalytic activity of PBzyme and further potentiate the effectiveness of tumor theranostics.