Structure-Switchable DNA Programmed Disassembly of Nanoparticles for Smart Size Tunability and Cancer-Specific Drug Release

The size of the nanocarrier is considered one of the most important issues for its therapeutic effect. Thus, an intelligent nanocarrier with dynamic size has been explored as a promising approach to fulfill the requirements for both efficient accumulation according to the enhanced penetration and retention (EPR) effect and deep penetration into tumor tissue. Herein, structure-switchable triplex DNA was modified on gold nanoparticles (AuNPs) to investigate its potential to modulate the nanoparticle dynamic disassembly process among the tumor microenvironment. We report that the pH-sensitive triplex DNA exhibited outstanding sensitivity and size tunability in triggering the disassembly of AuNP clusters into smaller sizes among the tumor acidic environment, leading to better permeability both in vitro and in vivo. By further combination of the telomerase-sensitive hairpin DNA loaded with chemotherapy drug doxorubicin (DOX), a cancer-specific intracellular drug-release function was also realized, resulting in a precise treatment effect and lower toxicity on normal cells. Through comodification of these two structure-switchable DNA chains on AuNPs and construction of nanoparticle assemblies with proper size, programmed disassembly and drug-release function in tissue and cell level, respectively, were successfully combined and eventually facilitated a highly efficient nanodrug transportation process, from tumor accumulation to deep penetration and precise cancer chemotherapy. The study provided the prospect of utilizing functionalized DNA in optimization of nanocarrier delivery efficiency.