Remote-Controlled Release of DNA in Living Cells via Simultaneous Light and Host–Guest Mediations

Using photons as external triggers to realize remote-controlled release of oligonucleotide is superior to other intracellular or external stimulus. UV light is a valid photon-controlled manner due to high efficiency. However, further applications of these approaches in living cells are hampered by the large dose of UV-light irradiation. To address this issue, a simultaneous light and host/guest mediation was proposed in this paper. Gold nanoparticles (AuNPs) encoding with mercapto-β-cyclodextrin (βCD) served as a carried agent. Azobenzene (Azo), which was labeled on a releasing oligonucleotide, acted as a photochemically controlled switch. Ferrocene (Fc), an excellent guest for inclusion complexation by βCD, serves as "enhancers" and shifts the equilibrium of the inclusion–exclusion process between trans-Azo and βCD under UV-light irradiation, thus making the dose of UV-light irradiation reduced obviously. For further application, transfected green fluorescent protein (GFP)-expressing human lung cancer A549 cells were used to determine cellular uptake and gene silencing mediated by our constructed system in vivo. The results demonstrate that by employing Fc host–guest interaction, about 62.4% gene silencing was achieved within 30 min, which is significantly higher than that without Fc competition. Our strategy provides the potential for orthogonal DNA delivery and therapeutic activation that would be capable of achieving higher levels of site-specific activity and reduced amounts of side effects.