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To date, few effective treatments have been licensed for nonalcoholic fatty liver disease (NAFLD), which a kind of chronic liver disease. Mammalian sterile 20-like kinase 1 (MST1) is reported to be involved in the development of NAFLD. Thus, we evaluated the suitability of a redox-unlockable polymeric nanoparticle Hep@PGEA vector to deliver MST1 or siMST1 (HCP/MST1 or HCP/siMST1) for NAFLD therapy. The Hep@PGEA vector can efficiently deliver the condensed functional nucleic acids MST1 or siMST1 into NAFLD-affected mouse liver to upregulate or downregulate MST1 expression. The HCP/MST1 complexes significantly improved liver insulin resistance sensitivity and reduced liver damage and lipid accumulation by the AMPK/SREBP-1c pathway without significant adverse events. Instead, HCP/siMST1 delivery exacerbates the NAFLD. The analysis of NAFLD patient samples further clarified the role of MST1 in the development of hepatic steatosis in patients with NAFLD. The MST1-based gene intervention is of considerable potential for clinical NAFLD therapy, and the Hep@PGEA vector provides a promising option for NAFLD gene therapy.

Chronic wounds cannot proceed through the normal, orderly, and timely sequence of repair. The adverse cycle between excess reactive oxide species (ROS) and a persistent inflammatory response is an important mechanism of impaired wound healing. Herein, by combining the intrinsic bioactivities of natural polysaccharides and natural drugs, a glycosaminoglycan-based hydrogel delivery system is proposed to regulate the wound microenvironment. Dynamic supramolecular cross-linking enables the hydrogel to easily encapsulate the drug and fully fill the wound area. As the backbone of the hydrogel, heparin captures inflammatory chemokines at the wound site, while hyaluronic acid mimics the function of ECM. The hydrophobic drug curcumin has been ingeniously encapsulated in the hydrogel through micellization, thereby exerting good ROS scavenging ability and anti-inflammatory activity. Evaluations in diabetic mice showed that this antioxidant and anti-inflammatory hydrogel was effective in reducing the influx of immune cells at the wound site and in down-regulating the inflammatory response. Accelerated wound healing was also observed, as evidenced by faster re-epithelialization and better ECM remodeling. The proposed hydrogel can regulate the microenvironment of wounds from multiple aspects and thereby achieve regression of wound repair, which may provide a new therapeutic strategy for chronic wounds.

Wearable pressure sensors are highly desirable for monitoring human health and realizing a nice human-machine interaction. Herein, a chitosan/MXene/polyurethane-sponge/polyvinyl alcohol (CS/MXene/PU sponge/PVA)-based 3D pressure sensor is developed to simultaneously achieve wearability, washability, and high sensitivity in a wide region. In the force-sensitive layer of the sensor, MXene and CS are fully attached to the PU sponge to ensure that the composite sponge has remarkable conductivity and washability. Benefiting from the highly resistive PVA-nanowire spacer, the initial current of the sensor is reduced significantly so that the sensor exhibits extremely high sensitivity (84.9 kPa-1 for the less than 5 kPa region and 140.6 kPa-1 for the 5-22 kPa region). Moreover, the sensor has an excellent fast response time of 200 ms and a short recovery time of 30 ms, as well as non-attenuating durability over 5000 cycles. With the high sensitivity in a wide range, the sensor is capable of detecting multiple human and animal activities in real time, ranging from the large pressure of joint activities to a subtle pressure of pulse. Furthermore, the sensor also demonstrates the potential application in measuring pressure distribution. Overall, such a multifunctional pressure sensor can supply a new platform for the design and development of wearable health-monitoring equipment and an efficient human-machine interface.

Inflammation has been assumed to affect the pathology of wound healing and is associated with many nonhealing chronic wounds. Naturally derived herbal medicines with anti-inflammatory properties are of interest because of their effectiveness and affordability in clinical treatment. Herein, we report a supramolecular hydrogel comprising self-assembled natural herb rhein and an oxidative responsive cross-linked network based on ferrocene and β-cyclodextrin host-guest recognitions. Rhein can directly self-assemble into fibrils, exerting better anti-inflammation efficiency than its free drug form. The adaption of the supramolecular network can greatly improve the stability and retain the structural integrity of encapsulated self-assembled rhein. In addition, host-guest recognition confers dissolution of the hydrogel under oxidative stress, thereby delivering self-assembled rhein to the wound site and exerting better therapeutic efficiency. Evaluations in diabetic mice indicate that the resultant hydrogel promoted chronic wound healing by suppressing excess reactive oxygen species, facilitating the transition of the wound healing process, and restoring the normal wound-repair process. Therefore, the proposed hydrogel has a potential value as an herbal-based dressing for future clinical chronic wound management.

Multifunctional antibacterial materials have great significance for treating biomedical device-associated infections (BAIs). In the present work, a facile and rational strategy was developed to produce dual-functional implants with antibacterial and osteointegration-promoting properties for the treatment of BAI. A titanium implant, as a representative demo of implants, was first functionalized with ethanediamine-functionalized poly(glycidyl methacrylate) (PGED) brushes. Then, low-molecular-weight quaternized polyethyleneimine (QPEI, a cationic antibacterial agent) and alendronate (ALN, a clinically used drug with high affinity for bone minerals) were covalently conjugated onto PGED brushes to produce dual-functional dental implants (Ti-AQ). The QPEI component imparted Ti-AQ with antibacterial abilities, and the ALN component could balance the cytotoxicity of a cationic antibacterial agent, improving the biocompatibility for osteoblast cells. The effective performances of anti-infection and osteointegration were demonstrated in a BAI animal model. The results indicated that Ti-AQ inhibited bacterial infection at the early stage and enhanced the osteointegration and biomechanical properties between the implants and bone tissues at the late stage. This study will provide one facile and universal strategy for the design and development of novel multifunctional antibacterial implants.

The development of new materials for fast and sensitive protease assay is in demand for timely diagnosis of diseases, such as cardiovascular disease, cancers, and Alzheimer disease. Herein, poly(methacrylic acid) (PMAA) brushes were synthesized from the surfaces of silica nanoparticles via surface-initiated atom transfer radical polymerization (ATRP), and functionalized with series of proteolytically cleavable peptides for highly sensitive protease assay. Upon the proteolytic cleavage of the peptides, a short peptide fragment with fluorescent tag (GGK-FITC) is released to the solution, which can be easily detected with a benchtop fluorescence microscope. The grafting densities of PMAA brushes and peptides can be readily tuned by controlling the monomer concentrations of sodium methacrylate in the ATRP reaction. Because of the three-dimensional architecture of PMAA brushes, the loading amount of peptides can reach 21.4% of the total weight of functionalized silica particles (22.4 peptides/nm2), which is mu...

Polysaccharide-based copolymers have attracted much attention due to their effective performances. Heparin, as a kind of polysaccharide with high negative charge densities, has attracted much attention in biomedical fields. In this work, we report a flexible way to adjust the solubility of heparin from water to oil via the introduction of tetrabutylammonium groups for further functionalization. A range of heparin-based comb copolymers with poly(poly(ethylene glycol) methyl ether methacrylate) (PPEGMEMA), poly(dimethylaminoethyl methacrylate) (PDMAEMA), or PPEGMEMA-b-PDMAEMA side chains were readily synthesized in a MeOH/dimethylsulfoxide mixture via atom-transfer radical polymerization. The heparin-based polymer nanoparticles involving cationic PDMAEMA were produced due to the electrostatic interaction between the negatively charged heparin backbone and PDMAEMA grafts. Then the pDNA condensation ability, cytotoxicity, and gene transfection efficiency of the nanoparticles were characterized in comparison with the reported gene vectors. The nanoparticles were proved to be effective gene vectors with low cytotoxicity and high transfection efficiency. This study demonstrates that by adjusting the solubility of heparin, polymer graft functionalization of heparin can be readily realized for wider applications.

Owing to the low cytotoxicity and excellent biocompatibility, polysaccharides are good candidates for the development of promising biomaterials. In this paper, a series of magnetic resonance imaging (MRI)-visible cationic polymeric nanoparticles involving liver cell-targeting polysaccharides were flexibly designed for multifunctional gene delivery systems. The pullulan-based vector (PuPGEA) consisting of one liver cell-targeting pullulan backbone and ethanolamine-functionalized poly(glycidyl methacrylate) (denoted by BUCT-PGEA) side chains with abundant hydroxyl units and secondary amine was first prepared by atom transfer radical polymerization. The resultant cationic nanoparticles (PuPGEA-GdL or PuPGEA-GdW) with MRI functions were produced accordingly by assembling PuPGEA with aminophenylboronic acid-modified Gd-DTPA (GdL) or GdW10O36(9-) (GdW) via the corresponding etherification or electrostatic interaction. The properties of the PuPGEA-GdL and PuPGEA-GdW nanoparticles including pDNA condensation ability, cytotoxicity, gene transfection, cellular uptake, and in vitro and in vivo MRI were characterized in details. Such kinds of cationic nanoparticles exhibited good performances in gene transfection in liver cells. PuPGEA-GdW demonstrated much better MRI abilities. The present design of PuPGEA-based cationic nanoparticles with the liver cell-targeting polysaccharides and MRI contrast agents would shed light on the exploration of tumor-targetable multifunctional gene delivery systems.

It was recently reported that ethanolamine-functionalized poly(glycidyl methacrylate) (PGEA) possesses great potential applications in gene therapy due to its good biocompatibility and high transfection efficiency. Importing responsivity into PGEA vectors would further improve their performances. Herein, a series of responsive star-shaped vectors, acetaled β-cyclodextrin-PGEAs (A-CD-PGEAs) consisting of a β-CD core and five PGEA arms linked by acid-labile acetal groups, were proposed and characterized as therapeutic pDNA vectors. The A-CD-PGEAs owned abundant hydroxyl groups to shield extra positive charges of A-CD-PGEAs/pDNA complexes, and the star structure could decrease charge density. The incorporation of acetal linkers endowed A-CD-PGEAs with pH responsivity and degradation. In weakly acidic endosome, the broken acetal linkers resulted in decomposition of A-CD-PGEAs and morphological transformation of A-CD-PGEAs/pDNA complexes, lowering cytotoxicity and accelerating release of pDNA. In comparison with control CD-PGEAs without acetal linkers, A-CD-PGEAs exhibited significantly better transfection performances.

Carbon nanotubes have excellent penetrability and encapsulation efficiency in the fields of drug and gene delivery. Because of their excellent physicochemical properties, biocompatible rodlike cellulose nanocrystals (CNCs) were reportedly expected to replace carbon nanotubes. In this work, CNCs from natural cotton wool were functionalized with disulfide bond-linked poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) brushes for effective biomedical applications. A range of CNC-graft-PDMAEMA vectors (termed as CNC-SS-PDs) with various molecular weights of PDMAEMA were synthesized. Under reducible conditions, PDMAEMA chains can be easily cleaved from CNCs. The gene condensation ability, reduction sensitivity, cytotoxicity, gene transfection, and in vivo antitumor activities of CNC-SS-PDs were investigated in detail. The CNC-SS-PDs exhibited good transfection efficiencies and low cytotoxicities. The needlelike shape of CNCs had an important effect on enhancing transfection efficiency. The antitumor effect of CNC-SS-PDs was evaluated by a suicide gene/prodrug system (cytosine deaminase/5-fluorocytosine, CD/5-FC) in vitro and in vivo. This research demonstrates that the functionalization of CNCs with redox-responsive polycations is an effective method for developing novel gene delivery systems.

The development of new cationic nanoparticles that are safe and effective for biomedical applications has attracted considerable attention. Low molecular weight polycations generally exhibit low toxicity; however, their poor efficiency in drug delivery systems hampers their application. In this work, a series of new low molecular weight 2,6-bis(1-methylbenzimidazolyl)pyridinyl (BIP)-terminated ethanolamine-functionalized poly(glycidyl methacrylate)s (BIP-PGEAs) were readily fabricated for effective codelivery of a gene and a drug. The BIP-PGEAs could form well-defined cationic nanoparticles (NPs) in an aqueous solution. They could effectively bind pDNA with an appropriate particle size and ζ-potential. More importantly, the BIP-PGEA NPs demonstrated much higher transfection efficiencies than linear PGEA (L-PGEA) and the traditional "gold-standard" branched polyethylenimine (25 kDa). Moreover, the BIP-PGEA NPs could effectively entrap a hydrophobic anticancer drug such as 10-hydroxy camptothecin (CPT). The synergistic antitumor effect of the BIP-PGEA-CPT NPs was demonstrated by employing a suicide gene therapy system, which contained cytosine deaminase and 5-fluorocytosine (CD/5-FC). The present strategy for preparing well-defined cationic nanoparticles from low-molecular-weight polycations could provide an intriguing method to produce new multifunctional, therapeutic NPs.

A robust prototypical anti-icing coating with a self-lubricating liquid water layer (SLWL) is fabricated via grafting cross-linked hygroscopic polymers inside the micropores of silicon wafer surfaces. The ice adhesion on the surface with SLWL is 1 order of magnitude lower than that on the superhydrophobic surfaces and the ice formed atop of it can be blown off by an action of strong breeze. The surface with self-lubricating liquid water layer exhibits excellent capability of self-healing and abrasion resistance. The SLWL surface should also find applications in antifogging and self-cleaning by rainfall, in addition to anti-icing and antifrosting.

High-molecular-weight comb-shaped cationic copolymers have been of interest and importance as nonviral gene delivery carriers. Poly(DL-aspartamide)-based biomaterials with good degradability and excellent biocompatibility could be used as the potential backbones of gene vectors. In this work, atom transfer radical polymerization (ATRP) was proposed to prepare the biocleavable and biodegradable comb-shaped poly(N-3-hydroxypropyl)aspartamide (PHPA)-based gene carriers. The bioreducible ATRP initiation sites were first introduced onto PHPA backbones. Then, the well-defined comb-shaped vectors (SS-PHPDs) consisting of degradable PHPD backbones and disulfide-linked cationic P(DMAEMA) side chains were produced for gene delivery. The P(DMAEMA) side chains were readily cleavable from the backbones under reducible conditions. The degradability of PHPA backbones would benefit the final removal of the gene carriers from the body.