Targeting and monitoring ovarian cancer invasion with an RNAi and peptide delivery system.

RNA interference (RNAi) therapeutics are an emerging class of medicines that selectively target mRNA transcripts to silence protein production and combat disease. Despite the recent progress, a generalizable approach for monitoring the efficacy of RNAi therapeutics without invasive biopsy remains a challenge. Here, we describe the development of a self-reporting, theranostic nanoparticle that delivers siRNA to silence a protein that drives cancer progression while also monitoring the functional activity of its downstream targets. Our therapeutic target is the transcription factor SMARCE1, which was previously identified as a key driver of invasion in early-stage breast cancer. Using a doxycycline-inducible shRNA knockdown in OVCAR8 ovarian cancer cells both in vitro and in vivo, we demonstrate that SMARCE1 is a master regulator of genes encoding proinvasive proteases in a model of human ovarian cancer. We additionally map the peptide cleavage profiles of SMARCE1-regulated proteases so as to design a readout for downstream enzymatic activity. To demonstrate the therapeutic and diagnostic potential of our approach, we engineered self-assembled layer-by-layer nanoparticles that can encapsulate nucleic acid cargo and be decorated with peptide substrates that release a urinary reporter upon exposure to SMARCE1-related proteases. In an orthotopic ovarian cancer xenograft model, theranostic nanoparticles were able to knockdown SMARCE1 which was in turn reported through a reduction in protease-activated urinary reporters. These LBL nanoparticles both silence gene products by delivering siRNA and noninvasively report on downstream target activity by delivering synthetic biomarkers to sites of disease, enabling dose-finding studies as well as longitudinal assessments of efficacy.

Advanced Functionalized Materials Based on Layer-by-Layer Assembled Natural Cellulose Nanofiber for Electrodes: A Review.

The depletion of fossil fuel resources and its impact on the environment provide a compelling motivation for the development of sustainable energy sources to meet the increasing demand for energy. Accordingly, research and development of energy storage devices have emerged as a critical area of focus. The electrode materials are critical in the electrochemical performance of energy storage devices, such as energy storage capacity and cycle life. Cellulose nanofiber (CNF) represents an important substrate with potentials in the applications of green electrode materials due to their environmental sustainability and excellent compatibility. By utilizing the layer-by layer (LbL) process, well-defined nanoscale multilayer structure is prepared on a variety of substrates. In recent years, increasing attention has focused on electrode materials produced from LbL process on CNFs to yield electrodes with exceptional properties, such as high specific surface area, outstanding electrical conductivity, superior electrochemical activity, and exceptional mechanical stability. This review provides a comprehensive overview on the development of functional CNF via the LbL approach as electrode materials.

Reversible Sensing Technologies Using Upcycled TPEE: Crafting pH and Light Responsive Materials towards Sustainable Monitoring.

Multiresponsive materials with reversible and durable characteristics are indispensable because of their promising applications in environmental change detections. To fabricate multiresponsive materials in mass production, however, complex reactions and impractical situations are often involved. Herein, a dual responsive (light and pH) spiropyran-based smart sensor fabricated by a simple layer-by-layer (LbL) assembly process from upcycled thermoplastic polyester elastomer (TPEE) materials derived from recycled polyethylene terephthalate (r-PET) is proposed. Positively charged chitosan solutions and negatively charged merocyanine-COOH (MC-COOH) solutions are employed in the LbL assembly technique, forming the chitosan-spiropyran deposited TPEE (TPEE-CH-SP) film. Upon UV irradiation, the spiropyran-COOH (SP-COOH) molecules on the TPEE-CH-SP film undergo the ring-opening isomerization, along with an apparent color change from colorless to purple, to transform into the MC-COOH molecules. By further exposing the TPEE-CH-MC film to hydrogen chloride (HCl) and nitric acid (HNO3) vapors, the MC-COOH molecules can be transformed into protonated merocyanine-COOH (MCH-COOH) with the simultaneous color change from purple to yellow.

Construction of Hierarchical Films via Layer-by-Layer Assembly of Exfoliated Unilamellar Zeolite Nanosheets.

Zeolites have been widely applied as versatile catalysts, sorbents, and ion exchangers with unique porous structures showing molecular sieving capability. In these years, it is reported that some layered zeolites can be delaminated into molecularly thin 2-dimensional (2D) nanosheets characterized by inherent porous structures and highly exposed active sites. In the present study, two types of zeolite nanosheets with distinct porous structures with MWW topology (denoted mww) and ferrierite-related structure (denoted bifer) are deposited on a substrate through the solution process via electrostatic self-assembly. Alternate deposition of zeolite nanosheets with polycation under optimized conditions allows the layer-by-layer growth of their multilayer films with a stacking distance of 2-3 nm. Furthermore, various hierarchical structures defined at the unit-cell dimensions can be constructed simply by conducting the deposition of mww and bifer nanosheets in a designed sequence. Adsorption of a dye, Rhodamine B, in these films, is examined to show that adsorption is dependent on constituent zeolite nanosheets and their assembled nanostructures. This work has provided fundamental advancements in the fabrication of artificial zeolite-related hierarchical structures, which may be extended to other zeolite nanosheets, broadening their functionalities, applications, and benefits.

Complex Sequence-Defined Heteropolymers Enable Controlled Film Growth in Layer-By-Layer Assembly.

Digitally-encoded poly(phosphodiesters) (d-PPDE) with highly complex primary structures are evaluated for layer-by-layer (LbL) assembly. To be easily decoded by mass spectrometry (MS), these digital polymers contain many different monomers: 2 coding units allowing binary encryption, 1 cleavable spacer allowing controlled MS fragmentation, and 3 mass tags allowing fragment identification. These complex heteropolymers are therefore composed of 6 different motifs. Despite this strong sequence heterogeneity, it is found that they enable a highly controlled LbL film formation. For instance, a regular growth is observed when alternating the deposition of negatively-charged d-PPDE and positively-charged poly(allyl amine hydrochloride) (PAH). Yet, in this approach, the interdistance between consecutive coded d-PPDE layers remains relatively small, which may be an issue for data storage applications, especially for the selective decoding of the stored information. Using poly(sodium 4-styrene sulfonate) (PSS) as an intermediate non-coded polyanion, it is shown that a controlled interdistance between d-PPDE layers can be easily achieved, while still maintaining a regular LbL growth. Last but not least, it is found in this work that d-PPDE of relatively small molecular weight (i.e., significantly smaller than those of PAH and PSS) still enables a controlled LbL assembly.

Synthesis, characterization and application of chitosan functionalized and functional graphene oxide membranes for desalination of water by pervaporation.

The use of graphene sheets in water treatment is increasing due to its adsorption capacity, reactivity, catalytic action and surface area. The challenges linked to wastewater treatment are vast due to the constant influx of various pollutants. Can the challenges of water desalination and purification be encountered by graphene-based composites and membranes?.The current work describes the synthesis of graphene oxide (GO) using modified Hummers' method. GO was functionalized with chitosan and used as adsorbents. On the other hand, it was reported that the surface of thin-film-composite (TFC) polyamide membranes was modified in order to desalinate highly saline water using pervaporation. The findings showed that GO synthesized by modified Hummers' method has a greater capacity for the adsorption of sodium ion and have better regeneration performance. Functionalization with chitosan increased adsorption capacity from 680.2 to 740.5 mg/g at the initial concentration of 45,000 mg/l of Na+ ions. On the other hand, modification in membrane comprises the chlorine treatment of surface of polyamide membrane. Layer-by-layer (LbL) deposition of positively charged polyethyleneimine (PEI) and negatively charged graphene oxide (GO) was followed. The PEI/GO LbL membrane's pure water flux was twice as high as compare to the original membrane. The synthesized membrane was tested against the aqueous solutions containing Na2SO4, MgSO4, NaCl and MgCl2 salts for their desalination. At different concentrations, a water flux of 8.9 kg/m2h with a huge salt rejection (>99.9%) was attained for every tested salt. It was observed that CS functionalized GO and GO membrane showed higher adsorption capacity and improved regeneration performance can be measured as an operational and active adsorbent for sea water desalination.

Adenosine Encapsulation and Characterization through Layer-by-Layer Assembly of Hydroxypropyl-ß-Cyclodextrin and Whey Protein Isolate as Wall Materials.

Adenosine, as a water-soluble active substance, has various pharmacological effects. This study proposes a layer-by-layer assembly method of composite wall materials, using hydroxypropyl-ß-cyclodextrin as the inner wall and whey protein isolate as the outer wall, to encapsulate adenosine within the core material, aiming to enhance adenosine microcapsules' stability through intermolecular interactions. By combining isothermal titration calorimetry with molecular modeling analysis, it was determined that the core material and the inner wall and the inner wall and the outer wall interact through intermolecular forces. Adenosine and hydroxypropyl-ß-cyclodextrin form an optimal 1:1 complex through hydrophobic interactions, while hydroxypropyl-ß-cyclodextrin and whey protein isolate interact through hydrogen bonds. The embedding rate of AD/Hp-ß-CD/WPI microcapsules was 36.80%, and the 24 h retention rate under the release behavior test was 76.09%. The method of preparing adenosine microcapsules using composite wall materials is environmentally friendly and shows broad application prospects in storage and delivery systems with sustained release properties.

Robust and Stable Atomically Precise Metal Nanoclusters Mediated Solar Water Splitting.

Atomically precise metal nanoclusters (NCs) represent an emerging sector of light-harvesting antennas by virtue of peculiar atomic stacking fashion, quantum confinement effect, and molecular-like discrete energy band structure. Nevertheless, precise control of charge carriers over metal NCs has yet to be achieved by the short carrier lifetime and intrinsic instability of metal NCs, which renders the complexity of metal NCs-based photosystems with photoredox mechanisms remaining elusive. Herein, fine tuning of charge migration over metal NCs is demonstrated by constructing directional charge transfer channels in multilayered heterostructure enabled by a facile layer-by-layer (LbL) assembly approach, wherein oppositely charged branched poly-ethylenimine (BPEI) and glutathione (GSH)-capped gold NCs [Aux NCs, Au25 (GSH)18 NCs] are alternately deposited on the metal oxide (MOs: TiO2 , WO3 , Fe2 O3 ) substrates. TheAux (Au25 ) NCs layer serves as light-harvesting antennas for engendering charge carriers, andBPEI interim layer uniformly intercalated at the interface of Aux NCs layer constitutes the tandem hole transport channel for motivating the charge transfer cascade, resulting in the considerably enhanced photoelectrochemical water oxidation performances. Besides, poor photo-stability of Aux NCs is surmounted by stimulating the hole transfer kinetics process.

Biomaterials for Hemostasis.

Uncontrolled bleeding is a major problem in trauma and emergency medicine. While materials for trauma applications would certainly find utility in traditional surgical settings, the unique environment of emergency medicine introduces additional design considerations, including the need for materials that are easily deployed in austere environments. Ideally, these materials would be available off the shelf, could be easily transported, and would be able to be stored at room temperature for some amount of time. Both natural and synthetic materials have been explored for the development of hemostatic materials. This review article provides an overview of classes of materials used for topical hemostats and newer developments in the area of injectable hemostats for use in emergency medicine.

A Multi-Pyridine-Anchored and -Linked Bilayer Photocathode for Water Reduction.

The development of efficient photocathodes is of critical importance for the constructions of promising tandem photo-electrochemical cells. Most known dye-sensitized photocathodes are prepared with the conventional carboxylic or phosphonic acid anchors and require the presence of other terminal linking groups to connect catalysts; they suffer from high synthetic difficulty and low adsorption stability in aqueous media. Here, a compact bilayer photocathode has been prepared by using a pyrene-based photosensitizer with multiple terminal pyridine moieties as both the anchoring and linking groups to connect a Co hydrogen-evolution catalyst to the NiO substrate. The catalyst and dye molecule are assembled in a layer-by-layer manner on NiO through the metal-pyridine coordination. This photocathode exhibits good dye adsorption stability in aqueous media. A stable cathodic photocurrent of 70 µA cm-2 was achieved, with H2 being generated at the photocathode under the visible-light irradiation. The Faraday efficiency of H2 evolution was estimated to be 9.1 %. Transient absorption spectral studies suggest that the interfacial hole transfer occurs within a few picoseconds. The integration of the organic photosensitizer with pyridine anchoring and linking groups is expected to provide a simple method for the fabrication of stable and efficient photocathodes.

Field-effect transistors engineered via solution-based layer-by-layer nanoarchitectonics.

The layer-by-layer (LbL) technique has been proven to be one of the most versatile approaches in order to fabricate functional nanofilms. The use of simple and inexpensive procedures as well as the possibility to incorporate a very wide range of materials through different interactions have driven its application in a wide range of fields. On the other hand, field-effect transistors (FETs) are certainly among the most important elements in electronics. The ability to modulate the flowing current between a source and a drain electrode via the voltage applied to the gate electrode endow these devices to switch or amplify electronic signals, being vital in all of our everyday electronic devices. In this topical review, we highlight different research efforts to engineer field-effect transistors using the LbL assembly approach. We firstly discuss on the engineering of the channel material of transistors via the LbL technique. Next, the deposition of dielectric materials through this approach is reviewed, allowing the development of high-performance electronic components. Finally, the application of the LbL approach to fabricate FETs-based biosensing devices is also discussed, as well as the improvement of the transistor's interfacial sensitivity by the engineering of the semiconductor with polyelectrolyte multilayers.

Stretchable Optical Diffuser Constructed by Alternate Procedure of Interfacial Complexation and Thermal Crosslinking.

Stretchable optical diffuser is an indispensable photon management element in wearable display devices. Herein, a novel optical diffuser constructed by interfacial hydrogen bonding complexation of methylcellulose (MC), poly(ethylene oxide) (PEO), and polymer complex nanoparticles (PCNP) on transparent polydimethylsiloxane (PDMS) substrate is proposed. The introduction of PEO can toughen the complex film and endow the coating with stretchability. With proper thermal treatment, the polymer complex can be crosslinked through esterification which shows an improved optical diffusion performance and durability. The optimized film exhibits 92% of transmittance (T), 93% of haze (H), and 73% of elongation. It also presents a desirable optical diffusion effect about 88% of T and 93% of H in the stretching state. Moreover, the resulting complex film shows excellent anti-fatigue capacity which maintains 90% of T and 90% of H after 10 000 stretching cycles. The reported polymer complex film broadens the application of interfacial complexation and demonstrates potential to apply in the integrated wearable optical devices.

Polymer/magnetite carriers functionalized by HER2-DARPin: Avoiding lysosomes during internalization and controlled toxicity of doxorubicin by focused ultrasound induced release.

Nanomedicine has revolutionized the available treatment options during the last decade, but poor selectivity of targeted drug delivery and release is still poses a challenge. In this study, doxorubicin (DOX) and magnetite nanoparticles were encapsulated by freezing-induced loading, coated with polymeric shell bearing two bi-layers of polyarginine/dextran sulphate and finally modified with HER2-specific DARPin proteins. We demonstrated that the enhanced cellular uptake of these nanocarriers predominantly occurs by SKOV-3 (HER2+) cells, in comparison to CHO (HER2-) cells, together with the controlled DOX release using low intensity focused ultrasound (LIFU). In addition, a good ability of DARPin+ capsules to accumulate in the tumor and the possibility of combination therapy with LIFU were demonstrated. A relatively high sensitivity of the obtained nanocarriers to LIFU and their preferential interactions with mitochondria in cancer cells make these carriers promising candidates for cancer treatment, including novel approaches to overcome drug resistance.

Unveiling the Assembly of Neutral Marine Polysaccharides into Electrostatic-Driven Layer-by-Layer Bioassemblies by Chemical Functionalization.

Marine-origin polysaccharides, in particular cationic and anionic ones, have been widely explored as building blocks in fully natural or hybrid electrostatic-driven Layer-by-Layer (LbL) assemblies for bioapplications. However, the low chemical versatility imparted by neutral polysaccharides has been limiting their assembly into LbL biodevices, despite their wide availability in sources such as the marine environment, easy functionality, and very appealing features for addressing multiple biomedical and biotechnological applications. In this work, we report the chemical functionalization of laminarin (LAM) and pullulan (PUL) marine polysaccharides with peptides bearing either six lysine (K6) or aspartic acid (D6) amino acids via Cu(I)-catalyzed azide-alkyne cycloaddition to synthesize positively and negatively charged polysaccharide-peptide conjugates. The successful conjugation of the peptides into the polysaccharide's backbone was confirmed by proton nuclear magnetic resonance and attenuated total reflectance Fourier-transform infrared spectroscopy, and the positive and negative charges of the LAM-K6/PUL-K6 and LAM-D6/PUL-D6 conjugates, respectively, were assessed by zeta-potential measurements. The electrostatic-driven LbL build-up of either the LAM-D6/LAM-K6 or PUL-D6/PUL-K6 multilayered thin film was monitored in situ by quartz crystal microbalance with dissipation monitoring, revealing the successful multilayered film growth and the enhanced stability of the PUL-based film. The construction of the PUL-peptide multilayered thin film was also assessed by scanning electron microscopy and its biocompatibility was demonstrated in vitro towards L929 mouse fibroblasts. The herein proposed approach could enable the inclusion of virtually any kind of small molecules in the multilayered assemblies, including bioactive moieties, and be translated into more convoluted structures of any size and geometry, thus extending the usefulness of neutral polysaccharides and opening new avenues in the biomedical field, including in controlled drug/therapeutics delivery, tissue engineering, and regenerative medicine strategies.

Reduced Graphene Oxide/Polyelectrolyte Multilayers for Fast Resistive Humidity Sensing.

Fast humidity sensors are of interest due to their potential application in new sensing technologies such as wearable personal healthcare and environment sensing devices. However, the realization of rapid response/recovery humidity sensors remains challenging primarily due to the sluggish adsorption/desorption of water molecules, which particularly impacts the response/recovery times. Moreover, another key factor for fast humidity sensing, namely the attainment of equal response and recovery times, has often been neglected. Herein, the layer-by-layer (LbL) assembly of a reduced graphene oxide (rGO)/polyelectrolyte is demonstrated for application in fast humidity sensors. The resulting sensors exhibit fast response and recovery times of 0.75 and 0.85 s (corresponding to times per RH range of 0.24 and 0.27 s RH-1, respectively), providing a difference of only 0.1 s (corresponding to 0.03 s RH-1). This performance exceeds that of the majority of previously reported graphene oxide (GO)- or rGO-based humidity sensors. In addition, the polyelectrolyte deposition time is shown to be key to controlling the humidity sensing kinetics. The as-developed rapid sensing system is expected to provide useful guidance for the tailorable design of fast humidity sensors.

Wafer-Scale Programmed Assembly of One-Atom-Thick Crystals.

Crystalline films offer various physical properties based on the modulation of their thicknesses and atomic structures. The layer-by-layer assembly of atomically thin crystals provides a powerful means to arbitrarily design films at the atomic level, which are unattainable with existing growth technologies. However, atomically clean assembly of the materials with high scalability and reproducibility remains challenging. We report programmed crystal assembly of graphene and monolayer hexagonal boron nitride, assisted by van der Waals interactions, to form wafer-scale films of pristine interfaces with near-unity yield. The atomic configurations of the films are tailored with layer-resolved compositions and in-plane crystalline orientations. We demonstrate batch-fabricated tunnel device arrays with modulation of the resistance over orders of magnitude by thickness control of the hexagonal boron nitride barrier with single-atom precision and large-scale, twisted multilayer graphene with programmable electronic band structures and crystal symmetries. Our results constitute an important development in the artificial design of large-scale films.

Photo-Degradable Protein-Polymer Hybrid Shells for Caging Living Cells.

There is growing demand for the precise remote control of cellular functions in various fields. Herein, a method for caging mammalian cells by coating with photodegradable protein-polymer hybrid shells to photo-control their functions without genetic engineering is reported. A layer-by-layer assembly of photocleavable synthetic materials through biotin-streptavidin (SA) binding was employed for cell coating. The cell surfaces were first biotinylated with photocleavable biotinylated poly(ethylene glycol)(PEG)-lipid and then coated by repeatedly layering SA and micelles of the PEG-lipid and photocleavable biotinylated four-arm PEG. The cell extension and adhesion were suppressed with the shells and then triggered with the degradation of the shells by light exposure. Macrophage phagocytosis was also stopped by caging with the shells and restarted by light-guided uncaging. This study provides the first proof of principle that cellular functions can be remotely controlled by steric hinderance of cell surfaces with photodegradable materials.

Advances in the application of chitosan as a sustainable bioactive material in food preservation.

Chitosan is obtained from chitin and considered to be one of the most abundant natural polysaccharides. Due to its functional activity, chitosan has received intense and growing interest in terms of applications for food preservation over the last half-century. Compared with earlier studies, recent research has increasingly focused on the exploration of preservation mechanism as well as the targeted inhibition with higher efficiency, which is fueled by availability of more active composite ingredients and integration of more technologies, and gradually perceived as "chitosan-based biofilm preservation." In this Review, we comprehensively summarize the potential antimicrobial mechanisms or hypotheses of chitosan and its widely compounded ingredients, as well as their impacts on endogenous enzymes, oxidation and/or gas barriers. The strategies used for enhancing active function of the film-forming system and subsequent film fabrication processes including direct coating, bioactive packaging film and layer-by-layer assembly are introduced. Finally, future development of chitosan-based bioactive film is also proposed to broaden its application boundaries. Generally, our goal is that this Review is easily accessible and instructive for whose new to the field, as well as hope to advance to the filed forward.

Preparation of chitosan-tannic acid coating and its anti-osteoclast and antibacterial activities in titanium implants.

INTRODUCTION: Bacterial infection and aseptic loosening caused by bone resorption at the implant interface are major clinical complications during bone defect implantation surgery, and surface modification of the implant to address the aforementioned problems has long been a research focus. MATERIALS AND METHODS: In this paper, a chitosan (CTS)-tannic acid (TA) colloid coating with a negative charge and excellent hydrophilicity was prepared on a Ti6Al4V (TC4) surface using a layer-by-layer assembly method. The physical properties, anti-osteoclast activity, and antimicrobial activity of the coatings were investigated. RESULTS: The findings showed that when the pH value was 5 and the ratio of CTS:TA was 0.8, the carrying rate of TA was the best. Furthermore, the CTS-TA coating had no cytotoxicity on the morphology and proliferation of BMSCs cells and effectively inhibited the differentiation of RAW264.7 cells into osteoclasts and the proliferation of Staphylococcus aureus and Escherichia coli. With the increase in the immersion time of TC4 in CTS-TA colloid solution, the inhibitory effects will also enhance. CONCLUSION: Therefore, the preparation of the CTS-TA coating provides a revolutionary technique for implant surface modification to avoid postoperative bacterial infection and aseptic loosening.

Layer-by-Layer Assembly of Multifunctional NR/MXene/CNTs Composite Films with Exceptional Electromagnetic Interference Shielding Performances and Excellent Mechanical Properties.

With the rapid advance of electronics, the light, flexible, and multifunctional composite films with high electromagnetic interference (EMI) shielding effectiveness and excellent thermal management are highly desirable for next-generation portable and wearable electronic devices. Herein, a series of flexible and ultrathin natural rubber/MXene/carbon nanotubes (NR/MXene/CNTs) composite films with sandwich structure are constructed layer by layer through a facile vacuum-assisted filtration method for EMI shielding and Joule heating application. The fabricated NR/MXene/CNTs-50 composite film, with NR/MXene as inner layer and NR/CNTs as out layers, not only has high EMI shielding efficiency, but also has excellent comprehensive mechanical properties at the thickness of only 200 µm. In addition, the superior environmental durability, high electrothermal conversion efficiency, hydrophobicity, and fine performance stability after periodic cyclic bending make the film possess more value in practical application.