Construction of a Single-Atom Nanozyme for Enhanced Chemodynamic Therapy and Chemotherapy

To fulfill the demand of precision and personalized medicine, single-atom catalysts (SACs) have emerged as a frontier in biomedical fields due to enzyme-mimic catalysis. Herein, we present a biocompatible and versatile nanoagent consisting of single-atom iron-containing nanoparticles (SAF NPs), DOX and A549 cell membrane (CM). The designed porous iron-based SACs originally served as a drug-carrying nanoplatform to release DOX selectively in a tumor microenvironment (TME) for chemotherapy (CT) due to their high loading capacity (155 %) for DOX; this signifies that SACs are promising candidates for universal cargo delivery. Besides, the designed single-atom nanoagent can perform like peroxidase, which effectively triggers an in situ tumor-specific Fenton reaction to generate abundant toxic hydroxyl radicals (⋅OH) selectively in the acidic TME for chemodynamic therapy (CDT). With the combination of CDT and CT, the constructed SAF NPs@DOX@CM nanoagent demonstrates better in vivo therapeutic performance than single-pathway therapy. In the meantime, after modification with CM, SAF NPs@DOX@CM can achieve homologous binding to target tumor tissues and avoid early clearance. This study presents a type of multifunctional SACs for enhanced cancer treatment via the capacity of a drug carrier combined with the enzymatic therapies of single-atom catalytic sites.