Engineering Seed-like Fe-Mn Nanomedicine with Ultrasmall Structure and ATP-Responsive Function for Tumor Metabolic and Redox Subversion

Sinceadenosine triphosphate (ATP) is an indispensable substancefor tumor survival, intracellular ATP regulation has emerged as acutting-edge antineoplastic strategy. Nevertheless, most ATP-responsiveanticancer nanomedicines are established with DNA structure, coordinatepolymer, and glucose oxidase as the core. Herein, in order to excavatethe design possibilities of ATP-responsive nanoplatforms, an ultrasmalliron (Fe)-manganese (Mn) nanomedicine (<5 nm) was designed by acombination of bottom-up and top-down approaches, employing Fe-basedreductant and Mn-based oxidant as raw materials. Due to the polyvalentFe/Mn states, as-prepared nanomedicine was featured with ATP, hydrogenperoxide (H2O2), and nicotinamide adenine dinucleotidephosphate (NADPH) reactivities to disrupt the metabolic and redoxhomeostasis of breast cancer and bone metastases sites. In addition,this nanomedicine was well-suited to offer dual-mode T-1/T-2 magnetic resonance imaging (MRI) for tumor detection.Therefore, this work provides a novel attempt for the exploitationof ultrasmall ATP-responsive antineoplastic nanomedicine.