Improved Cell Adhesion on Self-Assembled Chiral Nematic Cellulose Nanocrystal Films.

Chirality is ubiquitous in nature, and closely related to biological phenomena. Nature-originated nanomaterials such as cellulose nanocrystals (CNCs) are able to self-assemble into hierarchical chiral nematic CNC films and impart handedness to nano and micro scale. However, the effects of the chiral nematic surfaces on cell adhesion are still unknown. Herein, this work presents evidence that the left-handed self-assembled chiral nematic CNC films (L-CNC) significantly improve the adhesion of L929 fibroblasts compared to randomly arranged isotropic CNC films (I-CNC). The fluidic force microscopy-based single-cell force spectroscopy is introduced to assess the cell adhesion forces on the substrates of L-CNC and I-CNC, respectively. With this method, a maximum adhesion force of 133.2 nN is quantified for mature L929 fibroblasts after culturing for 24 h on L-CNC, whereas the L929 fibroblasts exert a maximum adhesion force of 78.4 nN on I-CNC under the same condition. Moreover, the instant SCFS reveals that the integrin pathways are involved in sensing the chirality of substrate surfaces. Overall, this work offers a starting point for the regulation of cell adhesion via the self-assembled nano and micro architecture of chiral nematic CNC films, with potential practical applications in tissue engineering and regenerative medicine.

Rapid Regulation of Cardiomyocytes Adhesion on Substrates with Varied Modulus via Mechanical Cues.

In-depth understanding of the mechanisms underlying the adhesion of myocardial cells holds significant importance for the development of effective therapeutic biomaterials aimed at repairing damaged or pathological myocardial tissues. Herein, we present evidence that myocardial cells (H9C2) exhibit integrin-based mechanosensing during the initial stage of adhesion (within the first 2 h), enabling them to recognize and respond to variations in substrate stiffnesses. Moreover, the bioinformatics analysis of RNA transcriptome sequencing (RNA-seq) reveals that the gene expressions associated with initial stage focal adhesion (Ctgf, Cyr61, Amotl2, Prickle1, Serpine1, Akap12, Hbegf, and Nedd9) are up-regulated on substrates with elevated Young's modulus. The fluorescent immunostaining results also suggest that increased substrate stiffness enhances the expression of Y397-phosphorylated focal adhesion kinase (FAK Y397), talin, and vinculin and the assembly of F-actin in H9C2 cells, thereby facilitating the adhesion of myocardial cells on the substrate. Next, we utilize fluidic force microscopy (FluidFM)-based single-cell force spectroscopy (SCFS) to quantitatively evaluate the impact of substrate stiffness on the cell adhesion force and adhesion work, thus providing novel insights into the biomechanical regulation of initial cell adhesion. Our findings demonstrate that the maximum adhesion forces of myocardial cells exhibit a rise from 23.6 to 248.0 nN when exposed to substrates with different moduli. It is worth noting that once the αvß3 integrins are blocked, the disparities in the adhesion forces of myocardial cells on these substrates become negligible. These results exhibit remarkable sensitivity of myocardial cells to mechanical cues of the substrate, highlighting the role of αvß3 integrin as a biomechanical sensor for the regulation of cell adhesion. Overall, this work offers a prospective approach for the regulation of cell adhesion via integrin mechanosensing with potential practical applications in the areas of tissue engineering and regenerative medicine.

Molecular Sizes and Antibacterial Performance Relationships of Flexible Ionic Liquid Derivatives.

Cationic agents, such as ionic liquids (ILs)-based species, have broad-spectrum antibacterial activities. However, the antibacterial mechanisms lack systematic and molecular-level research, especially for Gram-negative bacteria, which have highly organized membrane structures. Here, we designed a series of flexible fluorescent diketopyrrolopyrrole-based ionic liquid derivatives (ILDs) with various molecular sizes (1.95-4.2 nm). The structure-antibacterial activity relationships of the ILDs against Escherichia coli (E. coli) were systematically studied thorough antibacterial tests, fluorescent tracing, morphology analysis, molecular biology, and molecular dynamics (MD) simulations. ILD-6, with a relatively small molecular size, could penetrate through the bacterial membrane, leading to membrane thinning and intracellular activities. ILD-6 showed fast and efficient antimicrobial activity. With the increase of molecular sizes, the corresponding ILDs were proven to intercalate into the bacterial membrane, leading to the destabilization of the lipid bilayer and further contributing to the antimicrobial activities. Moreover, the antibacterial activity of ILD-8 was limited, where the size was not large enough to introduce significant membrane disorder. Relative antibacterial experiments using another common Gram-negative bacteria, Pseudomonas aeruginosa (PAO1), further confirmed the proposed structure-antibacterial activity relationships of ILDs. More impressively, both ILD-6 and ILD-12 displayed significant in vivo therapeutic effects on the PAO1-infected rat model, while ILD-8 performed poorly, which confirmed the antibacterial mechanism of ILDs and proved their potentials for future application. This work clarifies the interactions between molecular sizes of ionic liquid-based species and Gram-negative bacteria and will provide useful guidance for the rational design of high-performance antibacterial agents.

Gradient Functionalization of Various Quaternized Polyethylenimines on Microfluidic Chips for the Rapid Appraisal of Antibacterial Potencies.

The ability to appraise antibacterial potencies of surface-immobilized bactericidal polymers is still a major challenge in the engineering of antibacterial surfaces to combat hospital-acquired (nosocomial) infections. In this work, we fabricated a microfluidic platform with gradiently immobilized bactericidal polymers to enable the rapid appraisal of antibacterial potencies by in situ live/dead staining of bacteria. To this end, a variety of synthetic quaternary polymers, named QPEI-C1, QPEI-C6, QPEI-C8, and QPEI-C10, were gradiently immobilized in microfluidic channels, and their surface densities at different distances along the channels were quantified by using fluorescein-labeled polymers. We found that the surface densities of quaternary polymers could be well-tuned, and the length of the channel, resulting in a 50% reduction of live bacteria (L50), can be used to appraise the antibacterial potency of each bactericidal polymer. For instance, the L50 values of QPEI-C6-, QPEI-C8-, and QPEI-C10-modified channels against Escherichia coli were 35.5, 44.7, and 49.2 mm, respectively, indicating that QPEI-C10 exerted the most potent antibacterial efficacy. More importantly, this microfluidic platform enabled the rapid discrimination of antibacterial potencies of polymers (e.g., QPEI-C8, and QPEI-C10) while the conventional live/dead staining method found no significant difference. This work provides a powerful toolkit by combining advances of microfluidic systems and polymer science for the rapid screening of antibacterial coatings, which would find applications in surface modification of medical devices to combat bacterial infections.

Tunable Adhesion of Different Cell Types Modulated by Thermoresponsive Polymer Brush Thickness.

Tunable adhesion of different cell types on well-defined surfaces has attracted common interests in the field of biomaterial science and surface engineering. Herein, we demonstrate a new strategy for the regulation of cell adhesion by simply controlling the thickness of thermoresponsive poly(N-isopropylacrylamide) (PNIPAAm) brushes via surface-initiated atom transfer radical polymerization (ATRP). The adhesion of different cell types (4T1, HEK293, H9C2, HUVEC, and L929) can be easily modulated by varying the thickness of PNIPAAm brushes from 5.9 ± 1.0 nm (PN1) to 69.0 ± 5.0 nm (PN6). The fluorescent staining of different cell types on a variety of surfaces reveals that the thickness of PNIPAAm brushes would regulate the assembly of F-actin and the expression of vinculin and fibronectin, which are essential in regulating the adherent status of cells. Moreover, the cellular morphologies revealed that the adherent cells are well-spread, and multiple pseudopod extensions and protrusions can be observed at the margin of cells. This work provides a facile strategy for regulating tunable adhesion of different cell types, which may find applications in tissue engineering and regenerative medicine.

Antimicrobial Peptide-Conjugated Hierarchical Antifouling Polymer Brushes for Functionalized Catheter Surfaces.

Catheter-related infection is a great challenge to modern medicine, which causes significant economic burden and increases patient morbidity. Hence, there is a great requirement for functionalized surfaces with inherently antibacterial properties and biocompatibility that prevent bacterial colonization and attachment of blood cells. Herein, we developed a strategy for constructing polymer brushes with hierarchical architecture on polyurethane (PU) via surface-initiated atom-transfer radical polymerization (SI-ATRP). Surface-functionalized PU (PU-DMH) was readily prepared, which comprised of poly(3-[dimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]azaniumyl]propane-1-sulfonate) (PDMAPS) brushes as the lower layer and antimicrobial peptide-conjugated poly(methacrylic acid) (PMAA) brushes as the upper layer. The PU-DMH surface showed excellent bactericidal property against both Gram-positive and Gram-negative bacteria and could prevent accumulation of bacterial debris on surfaces. Simultaneously, the PU-DMH samples possessed good hemocompatibility and low cytotoxicity. Furthermore, the integrated antifouling and bactericidal properties of PU-DMH under hydrodynamic conditions were confirmed by an in vitro circulating model. The functionalized surface possessed persistent antifouling and bactericidal performances both under static and hydrodynamic conditions. The microbiological and histological results of animal experiments also verified the in vivo anti-infection performance. The present work might find promising clinical applications for preventing catheter-related infection.

NIR-Responsive Polycationic Gatekeeper-Cloaked Hetero-Nanoparticles for Multimodal Imaging-Guided Triple-Combination Therapy of Cancer.

Responsive multifunctional organic/inorganic nanohybrids are promising for effective and precise imaging-guided therapy of cancer. In this work, a near-infrared (NIR)-triggered multifunctional nanoplatform comprising Au nanorods (Au NRs), mesoporous silica, quantum dots (QDs), and two-armed ethanolamine-modified poly(glycidyl methacrylate) with cyclodextrin cores (denoted as CD-PGEA) has been successfully fabricated for multimodal imaging-guided triple-combination treatment of cancer. A hierarchical hetero-structure is first constructed via integration of Au NRs with QDs through a mesoporous silica intermediate layer. The X-ray opacity and photoacoustic (PA) property of Au NRs are utilized for tomography (CT) and PA imaging, and the imaging sensitivity is further enhanced by the fluorescent QDs. The mesoporous feature of silica allows the loading of a typical antitumor drug, doxorubicin (DOX), which are sealed by the polycationic gatekeepers, low toxic hydroxyl-rich CD-PGEA/pDNA complexes, realizing the co-delivery of drug and gene. The photothermal effect of Au NRs is utilized for photothermal therapy (PTT). More interestingly, such photothermal effect also induces a cascade of NIR-triggered release of DOX through the facilitated detachment of CD-PGEA gatekeepers for controlled chemotherapy. The resultant chemotherapy and gene therapy for glioma tumors are complementary for the efficiency of PTT. This work presents a novel responsive multifunctional imaging-guided therapy platform, which combines fluorescent/PA/CT imaging and gene/chemo/photothermal therapy into one nanostructure.

Ecotoxicity of two organophosphate pesticides chlorpyrifos and dichlorvos on non-targeting cyanobacteria Microcystis wesenbergii.

Organophosphate pesticides (OPs), as a replacement for the organochlorine pesticides, are generally considered non-toxic to plants and algae. Chlorpyrifos and dichlorvos are two OPs used for pest control all over the world. In this study, the dose-response of cyanobacteria Microcystis wesenbergii on OPs exposure and the stimulating effect of OPs with and without phosphorus source were investigated. The results showed that high concentrations of chlorpyrifos and dichlorvos caused significant decrease of chlorophyll a content. The median inhibitory concentrations (EC50) of chlorpyrifos and dichlorvos at 96 h were 15.40 and 261.16 µmol L(-1), respectively. Growth of M. wesenbergii under low concentration of OPs (ranged from 1/10,000 to 1/20 EC50), was increased by 35.85 % (chlorpyrifos) and 41.83 % (dichlorvos) at 120 h, respectively. Correspondingly, the highest enhancement on the maximum quantum yield (F v/F m) was 4.20 % (24 h) and 9.70 % (48 h), respectively. Chlorophyll fluorescence kinetics, known as O-J-I-P transients, showed significant enhancements in the O-J, J-I, and I-P transients under low concentrations of dichlorvos at 144 h, while enhancements of chlorophyll fluorescence kinetics induced by low concentrations of chlorpyrifos were only observed in the J-I transient at 144 h. Significant decreases of chlorophyll content, F v/F m and O-J-I-P transients with OPs as sole phosphorus source were found when they were compared with inorganic phosphate treatments. The results demonstrated an evidently hormetic dose-response of M. wesenbergii to both chlorpyrifos and dichlorvos, where high dose (far beyond environmental concentrations) exposure caused growth inhibition and low dose exposure induced enhancement on physiological processes. The stimulating effect of two OPs on growth of M. wesenbergii was negligible under phosphate limitation.

Sublethal toxic effects of nonylphenol ethoxylate and nonylphenol to Moina macrocopa.

The aim of this paper was to examine the sublethal toxic effects of nonylphenol ethoxylate (NP10EO), its primary degradation product nonylphenol (NP), and their mixture on Moina macrocopa. Chronic toxicity tests were carried out by using sublethal chemical concentrations. Results showed that all treatments reduced the survivorship, body length, and reproduction of M. macrocopa with NP being 10 %-20 % more toxic to M. macrocopa than NP10EO. Results also indicated that the toxic effects of NP10EO and NP mixture on M. macrocopa were more severe than that of any single chemical alone. At the highest concentration in this experiment, 0.337 mg L(-1) NP10EO plus 0.0154 mg L(-1) NP treatment caused the survivorship of M. macrocopa to zero, neonates number of reproductions to zero, 45.5 % reduction in the body length, and 88 % reduction in the total neonates number.

Progress and prospects in stem cell therapy.

In the past few years, progress being made in stem cell studies has incontestably led to the hope of developing cell replacement based therapy for diseases deficient in effective treatment by conventional ways. The induced pluripotent stem cells (iPSCs) are of great interest of cell therapy research because of their unrestricted self-renewal and differentiation potentials. Proof of principle studies have successfully demonstrated that iPSCs technology would substantially benefit clinical studies in various areas, including neurological disorders, hematologic diseases, cardiac diseases, liver diseases and etc. On top of this, latest advances of gene editing technologies have vigorously endorsed the possibility of obtaining disease-free autologous cells from patient specific iPSCs. Here in this review, we summarize current progress of stem cell therapy research with special enthusiasm in iPSCs studies. In addition, we compare current gene editing technologies and discuss their potential implications in clinic application in the future.

Antifungal effects of citronella oil against Aspergillus niger ATCC 16404.

Essential oils are aromatic oily liquids obtained from some aromatic plant materials. Certain essential oils such as citronella oil contain antifungal activity, but the antifungal effect is still unknown. In this study, we explored the antifungal effect of citronella oil with Aspergillus niger ATCC 16404. The antifungal activity of citronella oil on conidia of A. niger was determined by poisoned food technique, broth dilution method, and disc volatility method. Experimental results indicated that the citronella oil has strong antifungal activity: 0.125 (v/v) and 0.25 % (v/v) citronella oil inhibited the growth of 5 × 105 spore/ml conidia separately for 7 and 28 days while 0.5 % (v/v) citronella oil could completely kill the conidia of 5 × 105 spore/ml. Moreover, the fungicidal kinetic curves revealed that more than 90 % conidia (initial concentration is 5 × 105 spore/ml) were killed in all the treatments with 0.125 to 2 % citronella oil after 24 h. Furthermore, with increase of citronella oil concentration and treatment time, the antifungal activity was increased correspondingly. The 0.5 % (v/v) concentration of citronella oil was a threshold to kill the conidia thoroughly. The surviving conidia treated with 0.5 to 2 % citronella oil decreased by an order of magnitude every day, and no fungus survived after 10 days. With light microscope, scanning electron microscope, and transmission electron microscope, we found that citronella oil could lead to irreversible alteration of the hyphae and conidia. Based on our observation, we hypothesized that the citronella oil destroyed the cell wall of the A. niger hyphae, passed through the cell membrane, penetrated into the cytoplasm, and acted on the main organelles. Subsequently, the hyphae was collapsed and squashed due to large cytoplasm loss, and the organelles were severely destroyed. Similarly, citronella oil could lead to the rupture of hard cell wall and then act on the sporoplasm to kill the conidia. Nevertheless, the citronella oil provides a potential of being a safe and environmentally friendly fungicide in the future.

BODIPY-Functionalized Natural Polymer Coatings for Multimodal Therapy of Drug-Resistant Bacterial Infection.

The fact that multidrug resistance (MDR) could induce medical device-related infections, along with the invalidation of traditional antibiotics has become an intractable global medical issue. Therefore, there is a pressing need for innovative strategies of antibacterial functionalization of medical devices. For this purpose, a multimodal antibacterial coating that combines photothermal and photodynamic therapies (PTT/PDT) is developed here based on novel heavy atom-free photosensitizer compound, BDP-6 (a kind of boron-dipyrromethene). The photothermal conversion efficiency of BDP-6 is of 55.9%, which could improve biocompatibility during PTT/PDT process by reducing the exciting light power density. Furthermore, BDP-6, together with oxidized hyaluronic acid, is crosslinked with a natural polymer, gelatin, to fabricate a uniform coating (denoted as polyurethane (PU)-GHB) on the surface of polyurethane. PU-GHB has excellent synergistic in vitro PTT/PDT antibacterial performance against both susceptible bacteria and MDR bacteria. The antibacterial mechanisms are revealed as that hyperthermia could reduce the bacterial activity and enhance the permeability of inner membrane to reactive oxygen species by disturbing cell membrane. Meanwhile, in an infected abdominal wall hernia model, the notable anti-infection performance, good in vivo compatibility, and photoacoustic imaging property of PU-GHB are verified. A promising strategy of developing multifunctional antibacterial coatings on implanted medical devices is provided here.

Infection-responsive long-term antibacterial bone plates for open fracture therapy.

The infections in open fracture induce high morbidity worldwide. Thus, developing efficient anti-infective orthopedic devices is of great significance. In this work, we designed a kind of infection-responsive long-term antibacterial bone plates. Through a facile and flexible volatilization method, a multi-aldehyde polysaccharide derivative, oxidized sodium alginate, was crosslinked with multi-amino compounds, gentamycin and gelatin, to fabricate a uniform coating on Ti bone plates via Schiff base reaction, which was followed by a secondary crosslinking process by glutaraldehyde. The double-crosslinked coating was stable under normal condition, and could responsively release gentamycin by the triggering of the acidic microenvironment caused by bacterial metabolism, owning to the pH-responsiveness of imine structure. The thickness of the coating was ranging from 22.0 µm to 63.6 µm. The coated bone plates (Ti-GOGs) showed infection-triggered antibacterial properties (>99%) and high biocompatibility. After being soaked for five months, it still possessed efficient antibacterial ability, showing its sustainable antibacterial performance. The in vivo anti-infection ability was demonstrated by an animal model of infection after fracture fixation (IAFF). At the early stage of IAFF, Ti-GOGs could inhibit the bacterial infection (>99%). Subsequently, Ti-GOGs could promote recovery of fracture of IAFF. This work provides a convenient and universal strategy for fabrication of various antibacterial orthopedic devices, which is promising to prevent and treat IAFF.

Flexible Modulation of Cellular Activities with Cationic Photosensitizers: Insights of Alkyl Chain Length on Reactive Oxygen Species Antimicrobial Mechanisms.

Cationic photosensitizers have good binding ability with negatively charged bacteria and fungi, exhibiting broad applications potential in antimicrobial photodynamic therapy (aPDT). However, cationic photosensitizers often display unsatisfactory transkingdom selectivity between mammalian cells and pathogens, especially for eukaryotic fungi. It is unclear which biomolecular sites are more efficient for photodynamic damage, owing to the lack of systematic research with the same photosensitizer system. Herein, a series of cationic aggregation-induced emission (AIE) derivatives (CABs) (using berberine (BBR) as the photosensitizers core) with different length alkyl chains are successfully designed and synthesized for flexible modulation of cellular activities. The BBR core can efficiently produce reactive oxygen species (ROS) and achieve high-performance aPDT . Through the precise regulation of alkyl chain length, different bindings, localizations, and photodynamic killing effects of CABs are achieved and investigated systematically among bacteria, fungi, and mammalian cells. It is found that intracellular active substances, not membranes, are more efficient damage sites of aPDT. Moderate length alkyl chains enable CABs to effectively kill Gram-negative bacteria and fungi with light, while still maintaining excellent mammalian cell and blood compatibility. This study is expected to provide systematic theoretical and strategic research guidance for the construction of high-performance cationic photosensitizers with good transkingdom selectivity.

Reduction-responsive nucleic acid nanocarrier-mediated miR-22 inhibition of PI3K/AKT pathway for the treatment of patient-derived tumor xenograft osteosarcoma.

miRNAs are important regulators of gene expression and play key roles in the development of cancer, including osteosarcoma. During the development of osteosarcoma, the expression of miR-22 is significantly downregulated, making miR-22 as a promising therapeutic target against osteosarcoma. To design and fabricate efficient delivery carriers of miR-22 into osteosarcoma cells, a hydroxyl-rich reduction-responsive cationic polymeric nanoparticle, TGIC-CA (TC), was developed in this work, which also enhanced the therapeutic effects of Volasertib on osteosarcoma. TC was prepared by the ring-opening reaction between amino and epoxy groups by one-pot method, which had the good complexing ability with nucleic acids, reduction-responsive degradability and gene transfection performance. TC/miR-22 combined with volasertib could inhibit proliferation, migration and promote apoptosis of osteosarcoma cells in vitro. The anti-tumor mechanisms were revealed as TC/miR-22 and volasertib could inhibit the PI3K/Akt signaling pathway synergistically. Furthermore, this strategy showed outstanding tumor suppression performance in animal models of orthotopic osteosarcoma, especially in patient-derived chemo-resistant and chemo-intolerant patient-derived xenograft (PDX) models, which reduced the risk of tumor lung metastasis and overcame drug resistance. Therefore, it has great potential for efficient treatment of metastasis and drug resistance of osteosarcoma by the strategy of localized, sustained delivery of miR-22 using the cationic nanocarriers combined with non-traditional chemotherapy drugs.

Advances in constructing silver nanowire-based conductive pathways for flexible and stretchable electronics.

With their soaring technological demand, flexible and stretchable electronics have attracted many researchers' attention for a variety of applications. The challenge which was identified a decade ago and still remains, however, is that the conventional electrodes based on indium tin oxide (ITO) are not suitable for ultra-flexible electronic devices. The main reason is that ITO is brittle and expensive, limiting device performance and application. Thus, it is crucial to develop new materials and processes to construct flexible and stretchable electrodes with superior quality for next-generation soft devices. Herein, various types of conductive nanomaterials as candidates for flexible and stretchable electrodes are briefly reviewed. Among them, silver nanowire (AgNW) is selected as the focus of this review, on account of its excellent conductivity, superior flexibility, high technological maturity, and significant presence in the research community. To fabricate a reliable AgNW-based conductive network for electrodes, different processing technologies are introduced, and the corresponding characteristics are compared and discussed. Furthermore, this review summarizes strategies and the latest progress in enhancing the conductive pathway. Finally, we showcase some exemplary applications and provide some perspectives about the remaining technical challenges for future research.

A natural polysaccharide-based antibacterial functionalization strategy for liquid and air filtration membranes.

Filtration membranes are widely applied in medical fields. However, these membranes are challenged by bacterial contamination in hospitals, which increases the risk of nosocomial infections. Thus, it is significant to develop antibacterial filtration membranes. In this work, an oxidated dextran (ODex)-based antibacterial coating was designed and constructed on microfiltration (MF) membranes and melt-blown fabrics. Polyhexamethylene guanidine (PHMG) was synthesized as an antibacterial agent, and was fixed by ODex onto filtration membranes. The functionalized MF membranes increased the filtration efficiency for E. coli from 20.9% to 99.9%, and improved the absorption ratio for endotoxin by 59.1%, while the water flow rate still remained as high as 5255 L (h m2)-1. Furthermore, the trapped bacteria were inactivated by the antibacterial coating. For the melt-blown fabrics, the aerosol filtration efficiency was increased from 74.6% to 81.0%, and the antibacterial efficiency was promoted to 92.0%. The present work developed a facile and universal antibacterial functionalization strategy for filtration membranes, which provided a new method for the design and development of various novel antibacterial filtration materials in the medical field.

Fluorination of Polyethylenimines for Augmentation of Antibacterial Potency via Structural Damage and Potential Dissipation of Bacterial Membranes.

The rise of drug-resistant bacteria (e.g., methicillin-resistant Staphylococcus aureus, MRSA) has continued, making the ″super-bugs″ a formidable threat to global health. Herein, we synthesize a series of fluoroalkylated polyethylenimines (PEI-F) with different grafting degrees of fluoroalkyls via a simple ring-opening reaction and demonstrate for the first time that fluoroalkylated PEIs are able to exert potent antibacterial activity to Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Among the fluoroalkylated polymers, PEI-F3.0 shows the strongest antibacterial activity, with a minimum inhibitory concentration (MIC) of 64 µg mL-1, against both E. coli and S. aureus. More importantly, we find that PEI-F3.0 is able to kill over 99.8% of S. aureus within 1 min, which is extremely desirable for the treatment of acute and severe bacterial infections that require quick disinfection. We also demonstrate that the fluoroalkylated PEIs are able to kill bacteria via structural damage of the outer membrane (OM) and cytoplasmic membrane (CM), potential dissipation of CM, and generation of intracellular reactive oxygen species (ROS). The in vivo antibacterial test suggests that commercial Vaseline blended with 6.25 wt % of PEI-F3.0 (VL/PEI-F3.0) is able to efficaciously eradicate MRSA infection on a bacterial infected wound model and promote the healing procedure of the wound site. Therefore, the fluoroalkylated PEIs provide a promising strategy to cope with the major challenges of drug-resistant infections.

Derma-like antibacterial polysaccharide gel dressings for wound care.

Large skin wound infections have high morbidity, which threaten the health of human beings severely. It is essential to develop new wound dressings that can block microbial invasion, eliminate bacteria effectively, adhere to wounds firmly, and have good biocompatibility. In this work, we designed a kind of polysaccharide gel (DLG) dressings with derma-like structure that had good wound care performances. With a facile penetration cross-linking method by the Schiff base reaction between oxidized hyaluronic acid solution and carboxymethyl chitosan solution with higher viscosity, a gradient porous structure was formed inside DLG to mimic the structure of derma, which was due to the simultaneous penetration and reaction processes between two viscous solutions. This derma-like structure endowed the gel dressings with the abilities of self-adhesion to wounds and barriers against bacteria. Through the introduction of cuttlefish juice and gentamycin, the modified gel dressings (DLG-GS) showed mild photothermal effects under the near infrared irradiation at the wavelength of 808 nm, which could reach and maintain the temperature of 45 °C. The mild heat could act together with gentamycin to produce a rapid bactericidal performance within 5 min. Meanwhile, the polysaccharide gel dressings had good biocompatibility. The in vivo anti-infection properties of DLG-GS was demonstrated by an animal model of infected full-thickness skin defect. This strategy provided a feasible solution for the prevention and treatment of infected large wounds. STATEMENT OF SIGNIFICANCE: Derma-like antibacterial gel dressings (DLG-GS) with high bacterial barrier ability, strong tissue adhesive property and good biocompatibility were constructed by a penetration cross-linking method. DLG-GS could eliminate bacterial infection within 5 min due to the rational combination of a mild photothermal effect and antibiotics. DLG-GS showed high anti-infection and wound healing properties in an animal model of infected full-thickness skin defect. This study provides a flexible and universal strategy for the development  of antibacterial wound dressings.

Orchestrated Yolk-Shell Nanohybrids Regulate Macrophage Polarization and Dendritic Cell Maturation for Oncotherapy with Augmented Antitumor Immunity.

The protumoral and immunosuppressive tumor microenvironments greatly limit the antitumor immune responses of nanoparticles for cancer immunotherapy. Here, the intrinsic immunomodulatory effects of orchestrated nanoparticles and their ability to simultaneously trigger tumor antigen release, thereby reversing immunosuppression and achieving potent antitumor immunity and augmented cancer therapy, are explored. By optimizing both the composition and morphology, a facile strategy is proposed to construct yolk-shell nanohybrids (Fe3 O4 @C/MnO2 -PGEA, FCMP). The intrinsic immunomodulatory effects of FCMP are utilized to reprogram macrophages to M1 phenotype and induce the maturation of dendritic cells. In addition, the chemical, magnetic, and optical properties of FCMP contribute to amplified immunogenic cell death induced by multiaugmented chemodynamic therapy (CDT) and synergistic tumor treatment. Taking advantage of the unique yolk-shell structure, accurate T1 -T2 dual-mode magnetic resonance imaging can be realized and CDT can be maximized through sufficient exposure of both the Fe3 O4 core and MnO2 shell. Potent antitumor effects are found to substantially inhibit the growth of both primary and distant tumors. Furthermore, the strategy can be extended to the synthesis of other yolk-shell nanohybrids with tailored properties. This work establishes a novel strategy for the fabrication of multifunctional nanoplatforms with yolk-shell structure for effective cancer therapy with immunomodulation-enhanced antitumor immunity.