A Multifunctional Nanoplatform for Tumor-Targeted Imaging and Enhanced Ferroptosis Therapy

With the advantages of ferroptosis therapy (FT) in solving the apoptotic resistance of tumors, a smart strategy based on the combination of glucose oxidase (GOx) and ferroptosis-inducing nanoagents is proposed to boost the FT. However, most of the nanoagents remain limited in complex synthesis, poor targeting specificity, and unclarified biological mechanisms. Herein, a multifunctional nanoplatform based on fluorescent apoferritin-gold nanoclusters combined with GOx (AFt-AuNCs@GOx) is designed for tumor-targeted imaging and FT. The results show that AFt-AuNCs@GOx catalyze the generation of toxic center dot OH from H2O2 supplied by GOx. Consequently, AFt-AuNCs@GOx induce the enhanced ferroptosis effect in 4T1 cells. Additionally, the transcriptome assay of 4T1 cells identifies the differential expression genes related to ferroptosis process after AFt-AuNCs@GOx treatment. Moreover, with the merit of intrinsic fluorescence, the biodistribution both in vitro and in vivo of AFt-AuNCs@GOx can be effectively visualized. In vivo evidences reveal that AFt-AuNCs@GOx have the desired efficacy of FT and excellent biosafety. Overall, the AFt-AuNCs@GOx nanoplatform offer remarkable advantages in simple architecture, fluorescent imaging, precise targeting, and tumor inhibition. The exploration of the ferroptosis effect and biological mechanisms of AFt-AuNCs@GOx, as well as its application in tumor therapy, can introduce a new insight into the field of ferroptotic nanomedicine.