DNA Nanotechnology for Precise Control over Drug Delivery and Gene Therapy.

Nanomedicine has been growing exponentially due to its enhanced drug targeting and reduced drug toxicity. It uses the interactions where nanotechnological components and biological systems communicate with each other to facilitate the delivery performance. At this scale, the physiochemical properties of delivery systems strongly affect their capacities. Among current delivery systems, DNA nanotechnology shows many advantages because of its unprecedented engineering abilities. Through molecular recognition, DNA nanotechnology can be used to construct a variety of nanostructures with precisely controllable size, shape, and surface chemistry, which can be appreciated in the delivery process. In this review, different approaches that are currently used for the construction of DNA nanostructures are reported. Further, the utilization of these DNA nanostructures with the well-defined parameters for the precise control in drug delivery and gene therapy is discussed.

Valency-dependent affinity of bioactive hydroxyapatite-binding dendrons.

Hydroxyapatite (HA)-coated surfaces are used widely as stationary phase for protein and enzyme purification, coatings for dental and orthopedic implants, and composite materials for tissue engineering substrates. More advanced applications are envisioned, but progress has been slowed by the limited ability to controllably functionalize the surface of HA with biomolecules in a translationally relevant manner. Herein we report the synthesis and characterization of a series of multivalent, HA-binding peptide bioconjugates with variable valency and tether length which afford the ability to precisely tune the desired binding behavior. The respective binding affinities of the multivalent constructs to HA surface were characterized by quartz crystal microbalance with dissipation monitoring (QCM-D) techniques, and the relationship between dendron structure and binding affinity was revealed. Tetravalent constructs of HA-binding peptides show a 100-fold enhancement in binding affinity compared to HA-binding peptide sequences reported previously. Both biotin and bone morphogenic protein-2 (BMP-2) derivative peptide were successfully linked to the focal point as initial demonstrations.

Bioderived DNA Nanomachines for Potential Uses in Biosensing, Diagnostics, and Therapeutic Applications.

Beside its genomic properties, DNA is also recognized as a novel material in the field of nanoengineering. The specific bonding of base pairs can be used to direct the assembly of highly structured materials with specific nanoscale features such as periodic 2D arrays, 3D nanostructures, assembly of nanomaterials, and DNA nanomachines. In recent years, a variety of DNA nanomachines are developed because of their many potential applications in biosensing, diagnostics, and therapeutic applications. In this review, the fuel-powered motors and secondary structure motors, whose working mechanisms are inspired or derived from natural phenomena and nanomachines, are discussed. The combination of DNA motors with other platforms is then discussed. In each section of these motors, their mechanisms and their usage in the biomedical field are described. Finally, it is believed that these DNA-based nanomachines and hybrid motifs will become an integral point-of-care diagnostics and smart, site-specific therapeutic delivery.

Acoustically Propelled Nanomotors for Intracellular siRNA Delivery.

An effective intracellular gene silencing strategy based on acoustically propelled nanowires modified with an interfering RNA's (siRNA) payload is described. The gold nanowires (AuNW) are wrapped with a Rolling Circle Amplification (RCA) DNA strand, which serves to anchor the siRNA therapy. The ultrasound (US)-powered propulsion of the AuNW leads to fast internalization and rapid intracellular movement and hence to an accelerated siRNA delivery and silencing response. To optimize the micromotor gene silencing procedure, the influence of motion, time, and siRNA dosage was investigated, leading up to a 94% silencing after few minutes treatment with US-propelled siRNA-AuNWs, and to a dramatic (∼13-fold) improvement in the silencing response compared to the static modified nanowires. The ability of the nanomotor-based method for gene silencing has been demonstrated by measuring the GFP silencing response in two different cell lines (HEK-293 and MCF-7) and using detailed control experiments. The viability of the cells after the nanomotors treatment was examined using the MCF-7 cancer cell line. The use of DNA structures carried by the US-propelled nanomotors for gene silencing represents an efficient tool that addresses the challenges associated with RNA transportation and intracellular delivery. Future implementation of nanomachines in gene therapy applications can be expanded into a co-delivery platform for therapeutics.

Directed differentiation and neurite extension of mouse embryonic stem cell on aligned poly(lactide) nanofibers functionalized with YIGSR peptide.

End-functional PLLA nanofibers were fabricated into mats of random or aligned fibers and functionalized post-spinning using metal-free "click chemistry" with the peptide Tyr-Ile-Gly-Ser-Arg (YIGSR). Fibers that were both aligned and functionalized with YIGSR were found to significantly increase the fraction of mouse embryonic stem cells (mESC) expressing neuron-specific class III beta-tubulin (TUJ1), the level of neurite extension and gene expression for neural markers compared to mESC cultured on random fiber mats and unfunctionalized matrices. Precise functionalization of degradable polymers with bioactive peptides created translationally-relevant materials that capitalize on the advantages of both synthetic and natural systems, while mitigating the classic limitations of each.

Preparation of electrospun luminescent polyimide/europium nanofibers by simultaneous in situ sol-gel and imidization processes.

Luminescent polyimide (PI)/europium nanofibers have been successfully prepared by electrospinning combined with an in situ sol-gel technique. The possible reaction mechanism of the simultaneous imidization of polyamide acid and gelation of europium phase was analyzed by thermogravimetric analysis (TG) and differential scanning calorimetry (DSC). The results showed that chemical coupling and noncovalent interaction existed between the polymer and the europium which formed during the preparative process. Fourier-transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), and scanning electronic spectroscopy (SEM) studies also indicated the successful incorporation of europium into PI matrix and various morphologies could be achieved by controlling the calcination temperature and the europium content. Nanofibers with necklace-like structures were obtained after calcination under high temperatures. These PI/europium nanofibers were further demonstrated to have strong fluorescence emission. The intensity ratio for the PI/europium nanofibers, labeled as ((5)D(0)→(7)F(2))/((5)D(0)→(7)F(1)), which is well known as the asymmetry parameter, was lower than that in pure Eu(2)O(3) powder, indicating that there were highly symmetric coordination spheres around europium in the nanofibers.