Abstract
A DNA Origami-Gold Nanoparticle-Liposome Composite Nanostructure for Triggered Simultaneous Release of Multiple Drugs
Lipid-based drug carriers have shown great potential in delivering small molecule therapeutics and macromolecules such as nucleic acids. Despite great promise, current drug carriers deliver a single therapeutic payload and lack the ability to preferentially target disease sites and subsequently release their therapeutic payload in a controlled manner. In many cases of cancer, being able to deliver multiple drugs is desirable for efficacious treatment, but to date, these drugs have to be delivered sequentially. Here we harness the stability of DNA Origami structures and the thermal expansion functionality of gold nanoparticles to develop a lipid-based nanostructure capable of carrying a synergistic combination of drugs with the ability to trigger release only at the target site. This composite is generated through immobilization of a DNA Origami platform on a liposome surface. Positively charged gold nanoparticles are then “sandwiched” between two DNA Origami-liposome particles through electrostatic interactions of the DNA phosphate and charge on the gold particles. By enabling the simultaneous carriage and triggered release of drugs via our composite nanostructure, we can potentially increase antineoplastic effects of chemotherapeutics while reduce harmful side effects. Furthermore, the design of our system enables a high degree of adjustment and modularity. We could potentially adjust the proportion of the therapeutic payloads, the configuration of the structure, the main trigger and signal pair to adapt to various tissue environments, and all without affecting the stability of the primary drug carrying particle.
Special thanks to Lena Choi, Sophie Ebsary, Ileana Co, and Derek Chan for porting the old 2015 Weebly webpage into our new GitLab domain!