Arginine derivatives assist dopamine-hyaluronic acid hybrid hydrogels to have enhanced antioxidant activity for wound healing

The advent of genome editing has transformed the therapeutic landscape for several debilitating diseases, and the clinical outlook for gene therapeutics has never been more promising. The therapeutic potential of nucleic acids has been limited by a reliance on engineered viral vectors for delivery. Chemically defined polymers can remediate technological, regulatory, and clinical challenges associated with viral modes of gene delivery. Because of their scalability, versatility, and exquisite tunability, polymers are ideal biomaterial platforms for delivering nucleic acid payloads efficiently while minimizing immune response and cellular toxicity. While polymeric gene delivery has progressed significantly in the past four decades, clinical translation of polymeric vehicles faces several formidable challenges. The aim of our Account is to illustrate diverse concepts in designing polymeric vectors towards meeting therapeutic goals of in vivo and ex vivo gene therapy. Here, we highlight several classes of polymers employed in gene delivery and summarize the recent work on understanding the contributions of chemical and architectural design parameters. We touch upon characterization methods used to visualize and understand events transpiring at the interfaces between polymer, nucleic acids, and the physiological environment. We conclude that interdisciplinary approaches and methodologies motivated by fundamental questions are key to designing high-performing polymeric vehicles for gene therapy.

Polymeric Delivery of Therapeutic Nucleic Acids.

It has recently been found the graphene oxide (GO) aggregates form in cement paste due to the chemical cross-linking of calcium cations. Therefore, the effects of GO addition on the properties of cement based materials should be dependent on the properties of GO aggregates rather than GO nanosheets. In this study, GO aggregates were first characterized by particle size measurement. Then, the effects of GO aggregates on the degree of hydration, sorptivity, and tensile strength of cement paste were investigated. The aspect ratio of GO aggregates is much larger than that of the original GO nanosheets. Compared to plain cement paste, the increase of non-evaporable water content of the cement paste was found to be very limited, around 1.17% and 3.90% for cement pastes containing 0.02% and 0.04% by weight GO, respectively. The sorptivity of cement paste, especially the secondary sorptivity, was notably reduced for GO incorporated cement paste. The tensile strength was significantly improved by GO aggregates. Incorporation of 0.04% by weight GO increased the tensile strength by 67% compared to that of plain cement paste.

Effects of graphene oxide aggregates on hydration degree, sorptivity, and tensile splitting strength of cement paste

How the crowded environment inside cells affects the structures of proteins with aspherical shapes is a vital question because many proteins and protein–protein complexes in vivo adopt anisotropic shapes. Here we address this question by combining computational and experimental studies of a football-shaped protein (i.e., Borrelia burgdorferi VlsE) in crowded, cell-like conditions. The results show that macromolecular crowding affects protein-folding dynamics as well as overall protein shape. In crowded milieus, distinct conformational changes in VlsE are accompanied by secondary structure alterations that lead to exposure of a hidden antigenic region. Our work demonstrates the malleability of “native” proteins and implies that crowding-induced shape changes may be important for protein function and malfunction in vivo.

/pdf/crowded-cell-like-environment-induces-shape-changes-in-1npwt9n33s.pdf

Crowded, cell-like environment induces shape changes in aspherical protein

https://ris.utwente.nl/ws/files/30085981/1_s2.0_S0169409X17301072_main.pdf

Drug targeting to myofibroblasts: Implications for fibrosis and cancer

Graphene oxide (GO), as a typical two-dimensional material, possesses a range of oxygen-containing groups and shows surfactant and/or polyelectrolyte-like characteristics. Herein, GO sheets with narrow size distribution were prepared by an ultracentrifugation-based process and the aggregation behaviour of GO in pure water and an electrolyte aqueous solution were studied using laser light scattering (LLS). When adding common electrolytes, such as NaCl and MgCl2, into the GO dispersions, aggregation occurs and irreversible coagulation eventually occurs too. However, the GO dispersion can still remain stable when adding excess AlCl3. The zeta potential of the GO dispersion changes from negative to positive after the addition of access AlCl3, indicating that electrostatic repulsion is still responsible for the dispersion of GO, which is in good agreement with the LLS results. This finding on the dispersion of GO may be applied in the solution processing of GO. It also expands the scope of the design and preparation of new GO-based hybrid materials with different functions.

The dispersion and aggregation of graphene oxide in aqueous media

Human serum albumin (HSA) is the most abundant plasma protein and has an inherent ability to target tumor cells. It is an excellent candidate for drug delivery. However, HSA cannot form complex with DNA or RNA, because it is negatively charged under physiological conditions. In this work, we reported a simple method to prepare HSA/RNA nanoparticles mainly by physical interaction. Firstly, the solution pH is adjusted to 4.0, under which condition HSA is positively charged. It forms complex with RNA via electrostatic interaction. The solution is then heated at 75 oC for 15 min to stabilize the structure and the size of the formed complex. The HSA/RNA nanoparticle prepared by this method has a diameter about 110 nm and a narrow distribution. It is also stable for days under physiological conditions. Cellular essays demonstrate that these particles exhibit a high cellular uptake efficiency and non-toxicity to HeLa cells.

Encapsulation of RNA by negatively charged human serum albumin via physical interactions

The complexes formed by DNA or siRNA interacting with polycations showed great potential as nonviral vectors for gene delivery. The physicochemical properties of the DNA/siRNA complexes, which could be tuned by adjusting the characteristics of polycations, were directly related to their performance in gene delivery. Using 21 bp double-stranded oligonucleotide (ds-oligo) and two icosapeptides (with the repeating units being KKGG and KGKG, respectively) of the same charge density as model molecules, we investigated the effect of charge distribution on the kinetics of complexation and the structure of the final complexes. Even though the distribution of the charged groups in peptides was only adjusted by one position, the complexes formed by (KKGG)5 and ds-oligo were larger in size and easier to precipitate than those formed by (KGKG)5. Counterintuitively, it was not the charged groups but the hydrophilic neutral spacers that determined the kinetics and the structure of the complex. We attributed such an eff...

Effect of Peptide Charge Distribution on the Structure and Kinetics of DNA Complex

The structure and kinetics of the complex formed by hyaluronic acid (HA) and poly(L-lysine) (PLL) were studied by time-resolved laser light scattering, TEM, and AFM. Because HA has a hydrophilic backbone, the complexes formed by HA and PLL are different from those formed by oppositely charged polyelectrolytes both having hydrophobic backbones. Instead of forming strong aggregates and even precipitates, the complex in the presence of excess HA is stable in the studied time period. More importantly, the complex spontaneously forms core-corona structure by the rearrangement of HA chains. The core is composed of complex rich of PLL and the corona is mainly HA. Further analysis shows that the hydrogen bond formed by HA creates a barrier hindering the further relaxation of HA chains. The automatic formation of core-corona structure by PLL/HA is helpful not only to understand the relaxation of polyelectrolyte in complex, but also to develop drug carriers with desirable properties.

Core-Corona Structure Formed by Hyaluronic Acid and Poly(L-lysine) via Kinetic Path

The structure and stability of polyelectrolyte complex are controlled not only by electrostatic interaction but also by hydrogen bonding and hydrophobic interaction if they are present. The complexes formed by such multiple interactions should exhibit different responses to the environmental changes, such as ionic strength and pH. In this work, we designed a positively charged peptide S5R4, which can interact with poly(ethylene glycol)-block-poly(glutamate sodium) (PEG114-PGlu64) via electrostatic interaction, hydrogen bonding, and hydrophobic interaction. In deionized water at pH 7.1, the complexes formed by PEG114-PGlu64 and S5R4 assemble into wormlike micelles, spheres, and even hierarchical “wool balls”, depending on mixing ratio. However, a distinct dissociation–reassembly process is observed when 30 mM NaCl is added to screen the electrostatic interaction. The spheres transform into loose clusters after reassembly. This process is caused by the switch of driving force from electrostatic interaction ...

Assembly and Reassembly of Polyelectrolyte Complex Formed by Poly(ethylene glycol)-block-poly(glutamate sodium) and S5R4 Peptide

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