Ytterbium Doping-Retooled Prussian Blue for Tumor Metabolism Interference Therapy

Drug repurposing refers to excavating clinically approved drugs for new clinical indications, effectively shortening the cost and time of clinical evaluation due to the established molecular structure, pharmacokinetics, and pharmacodynamics. In this sense, clinically approved Prussian blue (PB) has received considerable attention, by virtue of its unique optical, magnetic, and enzymatic performance. Nevertheless, the clinical transformation of PB-based nanodrugs remains restricted owing to their complex synthetic formulation and constrained therapeutic performance. Herein, inspired by diagnostic and therapeutic superiorities of lanthanide ions, a series of ytterbium (Yb)-containing PB nanoparticles (NPs) are synthesized in one step through interstitial Yb-doping, which aims to improve the anticancer efficacy of PB and expand the biological application orientation of Yb ions. Through a systematic comparative analysis, involving microscopic morphology, size distribution, elemental composition, raw material utilization rate, and crystal structure, Yb-enriched PB NPs with better-balanced indexes are identified as an antineoplastic drug candidate. In parallel, their anticancer mechanisms are associated with the mammalian target of rapamycin (mTOR) and adenosine monophosphate-activated protein kinase (AMPK) pathways, thus disturbing anabolism, catabolism, and homeostasis. Therefore, this study attempts to implement the concept of drug repurposing and lays the foundation for next-generation theranostic nanodrugs.