Nonequilibrium Self-Assembly of Microtubules Through Stepwise Sequential Interactions of DNA.

The assembly of biological systems forms nonequilibrium patterns with different functionalities through molecular-level communication via stepwise sequential interaction and activation. The mimicking of this molecular signaling offers extensive opportunities to design self-assemblies of bioinspired synthetic nonequilibrium systems to develop molecular robots with active, adaptive, and autonomous behavior. Herein, the design and construction of biomolecular motor system, microtubule (MT)-kinesin based molecular swarm system, are reported through stepwise sequential interactions of DNA.

DNA Origami-Constructed Nanotapes for Sunitinib Adsorption and Inhibition of Renal Clear Carcinoma Cells.

Sunitinib (SUN) is a first-line drug for the treatment of renal clear carcinoma cells by targeting receptor tyrosine kinases (RTK) on the cell membrane. However, the effective delivery of SUN to the cell membrane remains a significant challenge. In this study, we fabricated precisely structured DNA nanotapes with strong surface SUN adhesion, enabling RTK inhibition of renal clear carcinoma cells.

Gelation upon the Mixing of Amphiphilic Graft and Triblock Copolymers Containing Enantiomeric Polylactide Segments through Stereocomplex Formation.

Biodegradable injectable polymer (IP) systems that form hydrogels in situ when injected into the body have considerable potential as medical materials. In this paper, we report a new two-solution mixed biodegradable IP system that utilizes the stereocomplex (SC) formation of poly(l-lactide) (PLLA) and poly(d-lactide) (PDLA). We synthesized triblock copolymers of PLLA and poly(ethylene glycol), PLLA--PEG--PLLA (-L), and a graft copolymer of dextran (Dex) attached to a PDLA--PEG diblock copolymer, Dex-g-(PDLA--PEG) (-D).

Development of immune cell delivery system using biodegradable injectable polymers for cancer immunotherapy.

Immune cell delivery using injectable hydrogel attracts much attention for improving its therapeutic effect. Specifically, dendritic cells (DCs) are the trigger cells for immune responses, and DC vaccines are studied for improving cancer immunotherapy. Hydrogel-assisted cell delivery is expected to enhance the viability of the implanted cells.

Synthesis of Topological Gels by Penetrating Polymerization Using a Molecular Net.

Topological gels possess structures that are cross-linked only via physical constraints; ideally, no attractive intermolecular interactions act between their components, which yields interesting physical properties. However, most reported previous topological gels were synthesized based on supramolecular interlocked structures such as polyrotaxane, for which attractive intermolecular interactions are essential. Here, we synthesize a water-soluble "molecular net" (MN) with a large molecular weight and three-dimensional network structure using poly(ethylene glycol).

Drug Delivery with Hyaluronic Acid-Coated Polymeric Micelles in Liver Fibrosis Therapy.

Developing delivery vehicles that achieve drug accumulation in the liver and transferability into hepatic stellate cells (HSCs) across the liver sinusoidal endothelium is essential to establish a treatment for hepatic fibrosis. We previously developed hyaluronic acid (HA)-coated polymeric micelles that exhibited affinity to liver sinusoidal endothelial cells. HA-coated micelles possess a core-shell structure of self-assembled biodegradable poly(l-lysine)--poly(lactic acid) AB-diblock copolymer (PLys--PLLA), and its exterior is coated with HA through polyion complex formation via electrostatic interaction between anionic HAs and cationic PLys segments.

Supramolecular enzyme-mimicking catalysts self-assembled from peptides.

Natural enzymes catalyze biochemical transformations in superior catalytic efficiency and remarkable substrate specificity. The excellent catalytic repertoire of enzymes is attributed to the sophisticated chemical structures of their active sites, as a result of billions-of-years natural evolution. However, large-scale practical applications of natural enzymes are restricted due to their poor stability, difficulty in modification, and high costs of production.

Preparation of hyaluronic acid-coated polymeric micelles for nasal vaccine delivery.

Hyaluronic acid (HA)-coated biodegradable polymeric micelles were developed as nanoparticulate vaccine delivery systems to establish an effective nasal vaccine. We previously reported HA-coated micelles prepared by forming a polyion complex (PIC) of poly(L-lysine)--polylactide (PLys--PLA) micelles and HA. The HA-coated micelles exhibited specific accumulation in HA receptor-expressing cells and extremely high colloidal stability under diluted blood conditions.

Postoperative Adhesion Prevention Using a Biodegradable Temperature-Responsive Injectable Polymer System and Concomitant Effects of the Chymase Inhibitor.

Postoperative adhesion remains a problem in surgery and causes postoperative complications. Laparoscopic surgery is now common, making it increasingly important to develop injectable formulations of adhesion barriers that can be applied during such surgeries. Temperature-responsive injectable polymer (IP) systems exhibiting a sol-to-gel transition in response to temperature are promising candidates as effective adhesion barriers that can be applied conveniently during laparoscopic surgery.

Temperature-responsive biodegradable injectable polymers with tissue adhesive properties.

Injectable polymers (IPs) exhibiting in situ hydrogel formation have attracted attention as vascular embolization and postoperative adhesion prevention materials. While utilizing hydrogels for such purposes, it is essential to ensure that they have appropriate and controllable tissue adhesion property, as it is crucial for them to not detach from their deposited location in the blood vessel or abdominal cavity. Additionally, it is important to maintain gel state in vivo for the desired period at such locations, where large amounts of body fluid exist.

Cellular therapy for myocardial ischemia using a temperature-responsive biodegradable injectable polymer system with adipose-derived stem cells.

Adipose-derived stem cell (AdSC) has been attracting attention as a convenient stem cell source. Not only AdSC can differentiate into various tissue cells, but it can also accelerate cell proliferation, anti-inflammation, and angiogenesis by secreting paracrine factors. Studies have demonstrated AdSC treatment of ischemic heart.

An intermolecular-split G-quadruplex DNAzyme sensor for dengue virus detection.

Nucleic acids have special ability to organize themselves into various non-canonical structures, including a four-stranded DNA structure termed G-quadruplex (G4) that has been utilized for diagnostic and therapeutic applications. Herein, we report the ability of G4 to distinguish dengue virus (DENV) based on its serotypes (DENV-1, DENV-2, DENV-3 and DENV-4) using a split G4-hemin DNAzyme configuration. In this system, two separate G-rich oligonucleotides are brought together upon target DNA strand hybridization to form a three-way junction architecture, allowing the formation of a G4 structure.

Single-Molecule AFM Study of DNA Damage by O Generated from Photoexcited C.

Light-induced oxidative damage of DNA by O generated from photoexcited C was observed at the single-molecule level by atomic force microscopy (AFM) imaging. Two types of DNA origami with uniform morphologies were immobilized on a mica surface and used as DNA substrates. Upon visible light irradiation (528 nm) in the presence of a C aqueous solution, the morphology changes of DNA origami substrates were observed by time-lapse AFM imaging at the single-molecule level by tracking a discrete DNA molecule.

Versatile Cell-Specific Ligand Arrangement System onto Desired Compartments of Biodegradable Matrices for Site-Selective Cell Adhesion Using DNA Tags.

A promising approach for the regeneration of tissues or organs with three-dimensional hierarchical structures is the preparation of scaffold-cell complexes that mimic these hierarchical structures. This requires an effective technique for immobilizing cell-specific ligands at arbitrarily chosen positions on matrices. Here, we report a versatile system for arranging cell-specific ligands onto desired compartments of biodegradable matrices for site-selective cell arrangement.

Reversible changes in the orientation of gold nanorod arrays on polymer brushes.

Nanoparticles exhibit a number of unique properties such as localized surface plasmon resonance (LSPR). As this LSPR is sensitive to geometrical or spatial conditions, the arrangement of nanoparticles, in particular the active arrangement of plasmonic structures, is an important issue. In this study, gold nanorod (GNR) arrays were prepared by GNR attachment on anionic polymer (DNA) brushes electrostatic interactions and their stimuli-responsive changes in orientation were investigated.

Cellular attachment behavior on biodegradable polymer surface immobilizing endothelial cell-specific peptide.

Small-caliber artificial blood vessels with inner diameters of smaller than 4 mm have not been put into practical use because of early thrombus formation and graft occlusion. To realize small-caliber artificial blood vessels with anti-thrombus property and long-term patency, one of the promising approaches is endothelialization of the lumen by tissue engineering approaches. Integrin α4β1 on the endothelial cell membrane is known to act as a receptor for Arg-Glu-Asp-Val (REDV) tetra-peptide, and this peptide can be used as a specific ligand to introduce endothelial cell attachment onto the surfaces of polymer scaffold.

Application of DNA Quadruplex Hydrogels Prepared from Polyethylene Glycol-Oligodeoxynucleotide Conjugates to Cell Culture Media.

Application of Na-responsive DNA quadruplex hydrogels, which utilize G-quadruplexes as crosslinking points of poly(ethylene glycol) (PEG) network as cell culture substrate, has been examined. PEG-oligodeoxynucleotide (ODN) conjugate, in which four deoxyguanosine (dG4) residues are tethered to both ends of PEG, was prepared by modified high-efficiency liquid phase (HELP) synthesis of oligonucleotides and used as the macromonomer. When mixed with equal volume of cell culture media, the solution of PEG-ODN turned into stiff hydrogel (G-quadruplex hydrogel) as the result of G-quadruplex formation by the dG4 segments in the presence of Na.

Artificial Smooth Muscle Model Composed of Hierarchically Ordered Microtubule Asters Mediated by DNA Origami Nanostructures.

DNA has been well-known for its applications in programmable self-assembly of materials. Nonetheless, utility of DNA origami, which offers more opportunity to realize complicated operations, has been very limited. Here we report self-assembly of a biomolecular motor system, microtubule-kinesin mediated by DNA origami nanostructures.

Control of swarming of molecular robots.

Recently we demonstrated swarming of a self-propelled biomolecular motor system microtubule (MT)-kinesin where interactions among thousands of motile MTs were regulated in a highly programmable fashion by using DNA as a processor. However, precise control of this potential system is yet to be achieved to optimize the swarm behavior. In this work, we systematically controlled swarming of MTs on kinesin adhered surface by different physicochemical parameters of MT-kinesin and DNA.

DNA Switch: Toehold-Mediated DNA Isothermal Amplification for Dengue Serotyping.

The inherent ability of nucleic acids to recognize a complementary pair has gained wide popularity in DNA sensor applications. DNA molecules can be produced in bulk and easily incorporated with various nanomaterials for sensing applications. More complex designs and sophisticated DNA sensors have been reported over the years to allow DNA detection in a faster, cheaper, and more convenient manner.

Preparation of Biodegradable Oligo(lactide)s-Grafted Dextran Nanogels for Efficient Drug Delivery by Controlling Intracellular Traffic.

Nanogels, nanometer-sized hydrogel particles, have great potential as drug delivery carriers. To achieve effective drug delivery to the active sites in a cell, control of intracellular traffic is important. In this study, we prepared nanogels composed of dextran with oligolactide (OLA) chains attached via disulfide bonds (Dex--SS-OLA) that collapse under the reductive conditions of the cytosol to achieve efficient drug delivery.

Bulk pH-Responsive DNA Quadruplex Hydrogels Prepared by Liquid-Phase, Large-Scale DNA Synthesis.

A new pH-responsive hydrogel biomaterial, that is composed of solely two popular biocompatible materials, oligodeoxynucleotides (ODN) and polyethylene glycol (PEG) have been prepared. Merely five deoxycytidine residues were elongated to the ends of linear or 4-arm PEG in ×1000 larger scale than conventional systems by using liquid-phase DNA synthesis technique, and applied them as a macromonomer for the preparation of hydrogels. The syntheses of the conjugates are simply elongating ODN onto the ends of PEG as a semisolid phase substrate using standard phosphoramidite chemistry.

DNA-assisted swarm control in a biomolecular motor system.

In nature, swarming behavior has evolved repeatedly among motile organisms because it confers a variety of beneficial emergent properties. These include improved information gathering, protection from predators, and resource utilization. Some organisms, e.