Supramolecular Modulator Assisted Cryo‐Engineered Porous Cu‐DNA Nano‐Vehicles for Versatile Theranostic Agent Delivery

Abstract

AbstractDNA nanotechnology combines structural design with therapeutic functions via programmable DNA motifs, but faces challenges in drug loading capacity. Herein a pore‐engineering strategy is reported to develop a highly porous, universal DNA nano‐vehicle through coordination self‐assembly, cryo‐engineering, and supramolecular chemistry, adapting to diverse cargo loading with desired theranostic agents. Thus, the complex synthesis and compatibility challenges typically associated with switching between different drug carriers are avoided. To this end, Cu2+ and nucleic acid therapeutic G3139 self‐assemble into a prefabricated solid nanostructure, which subsequently undergoes ultrafast freezing and sublimation to introduce porosity, forming highly porous Cu‐G3139 nanoparticles (CG NPs). The porous CG NPs efficiently accommodate diverse therapeutic molecules, from chemotherapeutics to non‐chemotherapeutic agents, facilitated by positively‐charged cyclodextrin. As a proof‐of‐concept, the photosensitizer indocyanine green (ICG) is loaded and coated with tannic acid (TA) to form CICG@TA, enabling remarkable photothermal and fluorescence imaging‐guided synergistic tumor ablation. This work represents the first demonstration of sublimation‐induced pore formation in metal‐DNA hybrid nanoparticles without chemical etching, offering a scalable “plug‐and‐play” platform for personalized cancer therapy without redesign. This versatile pore‐engineering strategy, merging supramolecular chemistry with cryo‐engineered porosity, opens up new avenues for efficient, customized multidrug delivery for diverse tumor theranostic applications.