Abstract
BackgroundControllable and multiple DNA release is critical in modern gene-based therapies. Current approaches require complex assistant molecules for combined release. To overcome the restrictions on the materials and environment, a novel and versatile DNA release method using a nano-electromechanical (NEMS) hypersonic resonator of gigahertz (GHz) frequency is developed.ResultsThe micro-vortexes excited by ultra-high frequency acoustic wave can generate tunable shear stress at solid–liquid interface, thereby disrupting molecular interactions in immobilized multilayered polyelectrolyte thin films and releasing embedded DNA strands in a controlled fashion. Both finite element model analysis and experiment results verify the feasibility of this method. The release rate and released amount are confirmed to be well tuned. Owing to the different forces generated at different depth of the films, release of two types of DNA molecules with different velocities is achieved, which further explores its application in combined gene therapy.ConclusionsOur research confirmed that this novel platform based on a nano-electromechanical hypersonic resonator works well for controllable single and multi-DNA release. In addition, the unique features of this resonator such as miniaturization and batch manufacturing open its possibility to be developed into a high-throughput, implantable and site targeting DNA release and delivery system.
Highlights
Controllable and multiple DNA release is critical in modern gene-based therapies
Liu et al [38] demonstrated a film fabrication method using a set of specially designed degradable cationic polymers performing different erosion speeds, which was applied to release two different plasmids with distinct profiles; Jessel et al [39] reported the use of cationic cyclodextrins as an enhancer for sequential and direct delivery of different DNA molecules into cells in contact with the films
Preparation of the LbL films Prior to film preparation, glass substrates and quartz crystal microbalance (QCM) chips were cleaned by 5 min rinsing in ethanol, 5 min rinsing in DI water, nitrogen-blow drying, and 20 min oxygen plasma treatment. 2 mg/ml PAH, 2 μM DNA, 28 mg/ml PSS and 10 mg/ml linear poly (LPEI) used for the fabrication of multilayered films were prepared in the presence of 150 mM NaCl
Summary
Controllable and multiple DNA release is critical in modern gene-based therapies. Current approaches require complex assistant molecules for combined release. Intense environmental changes required in certain release process may put forward a higher request for the protection of molecular bioactivity and restrict the application of the method in cell experiments and living organisms, and the adoption of some special materials in some cases to enhance the disruption may increase the complexity and cost of DNA immobilization. Another focus in the LbL-based release is the programmable release of multiple biological agents [34,35,36,37]. Developing DNA release method that can realize controllable and multiple release with simple and moderate disruption condition is in great demand
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