Self-assembled RNA interference microsponges for efficient siRNA delivery

The encapsulation and delivery of short interfering RNA (siRNA) has been realized using lipid nanoparticles1, 2, cationic complexes3, 4, inorganic nanoparticles5, 6, 7, 8, RNA nanoparticles9, 10 and dendrimers11. Still, the instability of RNA and the relatively ineffectual encapsulation process of siRNA remain critical issues towards the clinical translation of RNA as a therapeutic1, 12, 13. Here we report the synthesis of a delivery vehicle that combines carrier and cargo: RNA interference (RNAi) polymers that self-assemble into nanoscale pleated sheets of hairpin RNA, which in turn form sponge-like microspheres. The RNAi-microsponges consist entirely of cleavable RNA strands, and are processed by the cell’s RNA machinery to convert the stable hairpin RNA to siRNA only after cellular uptake, thus inherently providing protection for siRNA during delivery and transport to the cytoplasm. More than half a million copies of siRNA can be delivered to a cell with the uptake of a single RNAi-microsponge. The approach could lead to novel therapeutic routes for siRNA delivery.National Institutes of Health (U.S.) (NIH) NIBIB Grant R01-EB008082)United States. American Recovery and Reinvestment Act of 2009 ((ARRA) grant)National Science Foundation (U.S.) (Division of Materials Research Polymers Program grant #0705234)David H. Koch Institute for Integrative Cancer Research at MIT (Nanotechnology grant

Layer-by-Layer Assembled Antisense DNA Microsponge Particles for Efficient Delivery of Cancer Therapeutics

Antisense oligonucleotides can be employed as a potential approach to effectively treat cancer. However, the inherent instability and inefficient systemic delivery methods for antisense therapeutics remain major challenges to their clinical application. Here, we present a polymerized oligonucleotides (ODNs) that self-assemble during their formation through an enzymatic elongation method (rolling circle replication) to generate a composite nucleic acid/magnesium pyrophosphate sponge-like microstructure, or DNA microsponge, yielding high molecular weight nucleic acid product. In addition, this densely packed ODN microsponge structure can be further condensed to generate polyelectrolyte complexes with a favorable size for cellular uptake by displacing magnesium pyrophosphate crystals from the microsponge structure. Additional layers are applied to generate a blood-stable and multifunctional nanoparticle via the layer-by-layer (LbL) assembly technique. By taking advantage of DNA nanotechnology and LbL assembly, functionalized DNA nanostructures were utilized to provide extremely high numbers of repeated ODN copies for efficient antisense therapy. Moreover, we show that this formulation significantly improves nucleic acid drug/carrier stability during in vivo biodistribution. These polymeric ODN systems can be designed to serve as a potent means of delivering stable and large quantities of ODN therapeutics systemically for cancer treatment to tumor cells at significantly lower toxicity than traditional synthetic vectors, thus enabling a therapeutic window suitable for clinical translation.United States. Dept. of Defense. Ovarian Cancer Research Program (Teal Innovator Award Grant OC120504)Natural Sciences and Engineering Research Council of Canada (Postdoctoral Fellowship)National Institutes of Health (U.S.) (Ruth L. Kirschstein National Research Service Award 1F32EB017614-01)National Science Foundation (U.S.). Graduate Research Fellowshi

Layer-by-Layer Self-Assembled Ferrite Multilayer Nanofilms for Microwave Absorption

We demonstrate a simple method for fabricating multilayer thin films containing ferrite (Co0.5Zn0.5Fe2O4) nanoparticles, using layer-by-layer (LbL) self-assembly. These films have microwave absorbing properties for possible radar absorbing and stealth applications. To demonstrate incorporation of inorganic ferrite nanoparticles into an electrostatic-interaction-based LbL self-assembly, we fabricated two types of films: (1) a blended three-component LbL film consisting of a sequential poly(acrylic acid)/oleic acid-ferrite blend layer and a poly(allylamine hydrochloride) layer and (2) a tetralayer LbL film consisting of sequential poly(diallyldimethylammonium chloride), poly(sodium-4-sulfonate), bPEI-ferrite, and poly(sodium-4-sulfonate) layers. We compared surface morphologies, thicknesses, and packing density of the two types of ferrite multilayer film. Ferrite nanoparticles (Co0.5Zn0.5Fe2O4) were prepared via a coprecipitation method from an aqueous precursor solution. The structure and composition of the ferrite nanoparticles were characterized by X-ray diffraction, energy dispersive X-ray spectroscopy, transmission electron microscopy, and scanning electron microscopy. X-ray diffraction patterns of ferrite nanoparticles indicated a cubic spinel structure, and energy dispersive X-ray spectroscopy revealed their composition. Thickness growth and surface morphology were measured using a profilometer, atomic force microscope, and scanning electron microscope

Rapid Electromechanical Transduction on a Single-Walled Carbon Nanotube Film: Sensing Fast Mechanical Loading via Detection of Electrical Signal Change

Carbon nanotubes (CNTs) have been widely explored as next generation embedded-strain-pressure sensors. However, most investigations of CNT sensors did not consider the response time as a critical factor, although the ultrafast sensing of mechanical deformation is very important for the detection of dynamic loading or impact, such as in reactive armor systems. Owing to the low capacitance that shortens the response time of the electrical resistance changes induced by mechanical deformation, CNTs are expected to detect rapid electromechanical transduction without delay. Herein, we fabricate single-walled carbon nanotube (SWNT) films on diverse substrates, and evaluate their applications as sensors to detect rapid electromechanical transduction on a macroscopic scale. Under repetitive, high-speed mechanical loading, the SWNT films generate consistent electrical signal changes, which are accurately synchronized with their strain and the beginning of the deformation

Layer-by-layer assembled polymeric thin films as prospective drug delivery carriers: design and applications

Abstract Background The main purpose of drug delivery systems is to deliver the drugs at the appropriate concentration to the precise target site. Recently, the application of a thin film in the field of drug delivery has gained increasing interest because of its ability to safely load drugs and to release the drug in a controlled manner, which improves drug efficacy. Drug loading by the thin film can be done in various ways, depending on type of the drug, the area of exposure, and the purpose of drug delivery. Main text This review summarizes the various methods used for preparing thin films with drugs via Layer-by-layer (LbL) assembly. Furthermore, additional functionalities of thin films using surface modification in drug delivery are briefly discussed. There are three types of methods for preparing a drug-carrying multilayered film using LbL assembly. First methods include approaches for direct loading of the drug into the pre-fabricated multilayer film. Second methods are preparing thin films using drugs as building blocks. Thirdly, the drugs are incorporated in the cargo so that the cargo itself can be used as the materials of the film. Conclusion The appropriate designs of the drug-loaded film were produced in consideration of the release amounts and site of the desired drug. Furthermore, additional surface modification using the LbL technique enabled the preparation of effective drug delivery carriers with improved targeting effect. Therefore, the multilayer thin films fabricated by the LbL technique are a promising candidate for an ideal drug delivery system and the development possibilities of this technology are infinite

Spontaneous Biomacromolecule Absorption and Long-Term Release by Graphene Oxide

Biomacromolecule loading is the popular research in the biomedical field. To control the loading amount and releasing profile, various materials and fabrication techniques were developed. In this study, layer-by-layer assembly of multilayer films between collagen (Col) and graphene oxide (GO) was used to control the release of the loading molecule. By mixing GO into the system, ovalbumin (OVA) can be spontaneously adsorbed onto the GO sheet (denoted as GO/OVA) via the hydrophobic interaction. Two kinds of multilayer films (Col/GO/OVA and Col/GO/OVA) were fabricated. The thickness growth curve, quantitative of each layer adsorption, film morphology, stability, cell viability, and OVA release from multilayer films were investigated. The result has shown excellent film stability, macromolecule loading, and sustained release because of GO ability