Size-Tunable Assemblies Based on Ferrocene-Containing DNA Polymers for Spatially Uniform Penetration

Polymeric assemblies in the range of 100 nm can accumulate effectively around tumor tissue via the enhanced permeability and retention (EPR) effect. However, the desirable diameter for spatially uniform penetration is less than 30 nm, conflicting with requirements specified for the EPR effect. Here, a ferrocene-containing nucleic acid polymer was designed, and a size-tunable assembly system was developed to resolve the conflict between the EPR effect and spatially uniform penetration. Specifically, assemblies in the range of 100 nm can accumulate around the tumor via the EPR effect rapidly. After exposure to the tumor microenvironment, ferrocene moieties in this assembly can undergo a Fenton-like reaction that results in remarkable size shrinkage to 10 nm, thereby improving the tumor penetration ability of the assembly. These nucleic acid assemblies can also release highly toxic hydroxyl radicals into the tumor microenvironment, achieving in vivo catalytic therapy for efficient cancer treatment.