Surface-mediated nucleic acid delivery by lipoplexes prepared in microwell arrays

Many delivery methods have been developed to improve the therapeutic efficacy and facilitate the clinical translation of nucleic acid-based therapeutics. A facile surface-mediated nucleic acid delivery by lipoplexes is prepared in a microwell array, which combines the advantages of lipoplexes as an efficient carrier system, surface-mediated delivery, and the control of surface topography. Uniform disc-like lipoplexes containing nucleic acids are formed in the microwell array with a diameter of ∼818 nm and thickness of ∼195 nm. The microwell array-mediated delivery of lipoplexes containing FAM-oligodeoxynucleotides is ∼18.6 and ∼10.6 times more efficient than the conventional transfection method in an adherent cell line (A549 non-small cell lung cancer cells) and a suspension cell line (KG-1a acute myelogenous leukemia cells), respectively. MicroRNA-29b is then used as a model nucleic acid to investigate the therapeutic efficacy of lipoplexes delivered by the microwell array. Compared to conventional transfection methods, the effective therapeutic dosage of microRNA-29b is reduced from the microgram level to the nanogram level by lipoplexes prepared in the microwell array. The microwell array is also a very flexible platform. Both nucleic acid therapeutics and imaging reagents are incorporated in lipoplexes and successfully delivered to A549 cells, demonstrating its potential applications in theranostic medicine. Uniform lipoplexes containing nucleic acids are prepared in a microwell array by discontinuous dewetting in a facile and well controlled manner. The microwell array-mediated delivery of lipoplexes containing nucleic acids is more efficient than a conventional transfection method, and thus significantly enhances the therapeutic efficacy at much lower effective doses of therapeutic reagents. Microwell arrays are also a very flexible platform that can be used to deliver multifunctional lipoplexes for applications in theranostic medicine.