DNA-Liposome Hybrid Carriers for Triggered Cargo Release

The encapsulation of chemotherapeutics by biocompatible carrier structures holds great promise to preserve their therapeutic activity and favor their delivery to tumor sites. To enhance the bioavailability of a drug at the targeted tissue, triggered release mechanisms have received increasing research interest. Many approaches rely on exogeneous triggers such as the irradiation of ultrasound, visible or even ionizing electromagnetic waves. However, such exogenous triggers can be challenging to implement in a specific manner. Therefore, designing carriers responsive to endogenous moieties, such as nucleic acid biomarkers, is a desirable step in the search of personalized drug delivery nanoplatforms. This study presents an approach to building a biocompatible DNA-liposome hybrid nanocarrier for potential triggered release purposes. We form a DNA mesh on large unilamellar liposomes incorporating a trigger-responsive DNA building block. Upon incubation with a single-stranded DNA trigger sequence a hairpin closes and the building block is allowed to self-contract. By this process, we demonstrate elevated release of the dye calcein and the drug doxorubicin. The incubation of the doxorubicin-laden active hybrid carrier with HEK293T cells suggests increased cytotoxicity relative to a control carrier without the triggered release mechanism. In the future, the trigger could be provided by peritumoral nucleic acid sequences and lead to site-selective release of encapsulated chemotherapeutics.