DNA-Liposome Hybrid Carriers for Triggered Cargo Release

The design of simple and versatile synthetic routes to accomplish triggered-release properties in carriers is of particular interest for drug delivery purposes. In this context, the programmability and adaptability of DNA nanoarchitectures in combination with liposomes have great potential to render biocompatible hybrid carriers for triggered cargo release. We present an approach to form a DNA mesh on large unilamellar liposomes incorporating a stimuli-responsive DNA building block. Upon incubation with a single-stranded DNA trigger sequence, a hairpin closes, and the DNA building block is allowed to self-contract. We demonstrate the actuation of this building block by single-molecule Förster resonance energy transfer (FRET), fluorescence recovery after photobleaching, and fluorescence quenching measurements. By triggering this process, we demonstrate the elevated release of the dye calcein from the DNA–liposome hybrid carriers. Interestingly, 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.
The research leading to these results has received funding from the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007-2013) through the ERC grant PhysProt (Agreement No. 337969). K.N.B., P.S.C., and T.P.J.K. are grateful for financial support from the Biotechnology and Biological Sciences Research Council (BBSRC), the Newman Foundation, the Wellcome Trust, and the Cambridge Centre for Misfolding Diseases. D.M. is supported by the Winton Programme for the Physics of Sustainability, as well as the Engineering and Physical Sciences Research Council (EPSRC). P.T. gratefully acknowledges funding by the Bavarian Ministry of Science and the Arts through the ONE MUNICH Project “Munich Multiscale Biofabrication” and by the LMU-Cambridge strategic partnership. S.H.A. acknowledges funding by the Gobierno de Aragón-FSE (Research Group E47_20R).