MXene-based polysaccharide aerogel with multifunctional enduring antimicrobial effects for infected wound healing.

Wound infection is a predominant etiological factor contributing to delayed wound healing in open wounds. Hence, it holds paramount clinical significance to devise wound dressings endowed with superior antibacterial properties. In this study, a Schiff base-crosslinked aerogel comprising sodium alginate oxide (OSA), carboxymethyl chitosan (CMCS), and Nb2C@Ag/PDA (NAP) was developed. The resultant OSA/CMCS-Nb2C@Ag/PDA (OC/NAP) composite aerogel exhibited commendable attributes including exceptional swelling characteristics, porosity, biocompatibility, and sustained antimicrobial efficacy. In vitro antimicrobial assays unequivocally demonstrated that the OC/NAP composite aerogel maintained nearly 100 % inhibition of Staphylococcus aureus and Escherichia coli under an 808 nm laser even after 25 h. Crucially, the outcomes of in vivo infected wound healing experiments demonstrated that the wound healing rate of the OC/NAP composite aerogel group reached approximately 100 % within a span of 14 days, which was significantly greater than that of the blank control group. In vitro and in vivo hemostatic experiments also revealed that the composite aerogel had excellent hemostatic properties. The results of this study demonstrate the remarkable potential of OC/NAP aerogel as a multifunctional clinical wound dressing, especially for infected wounds.

Lipid-Polymer Hybrid Nanoparticles with Both PD-L1 Knockdown and Mild Photothermal Effect for Tumor Photothermal Immunotherapy.

In developing countries, the incidence of colorectal cancer (CRC) is on the rise. The combination of programmed cell death ligand-1 (PD-L1) siRNA (siPD-L1) and mild photothermal therapy (PTT) is a promising strategy for CRC treatment. In this study, dopamine-modified polyethylenimine (PEI) was prepared to fabricate an IR780 and siPD-L1 codelivery lipid-polymer hybrid nanoparticle (lip@PSD-siP) for the photothermal immunotherapy of CRC. The modification of dopamine can significantly reduce the cytotoxicity of PEI. lip@PSD-siP can be effectively taken up by CT26 cells and successfully escaped from lysosomes after entering the cells for 4 h. After CT26 cells were transfected with lip@PSD-siP, the PD-L1 positive cell rate decreased by 82.4%, and its PD-L1 knockdown effect was significantly stronger than the positive control Lipo3000-siP. In vivo studies showed that lip@PSD-siP-mediated mild PTT and efficient PD-L1 knockdown exhibited primary and distal tumor inhibition, metastasis delay, and rechallenged tumor inhibition. The treatment with lip@PSD-siP significantly promoted the maturation of dendritic cells in lymph nodes. The amount of T cell infiltration in the tumor tissues increased significantly, and the frequency of CD8+ T cells and CD4+ T cells was significantly higher than that of other groups. The percentage of immunosuppressive regulatory cells (Tregs) in the tumor tissue on the treatment side decreased by 88% compared to the PBS group, and the proportion of CD8+CD69+ T cells in the distal tumor tissue was 2.8 times that of the PBS group. The memory T cells of mice in the long-term antitumor model were analyzed. The results showed that after treatment with lip@PSD-siP, the frequency of effector memory T cells (Tem cells) significantly increased, suggesting the formation of immune memory.

Polydopamine-coated i-motif DNA/Gold nanoplatforms for synergistic photothermal-chemotherapy.

The combination of photothermal therapy with chemotherapy has gradually developed into promising cancer therapy. Here, a synergistic photothermal-chemotherapy nanoplatform based on polydopamine (PDA)-coated gold nanoparticles (AuNPs) were facilely achieved via the in situ polymerization of dopamine (DA) on the surface of AuNPs. This nanoplatform exhibited augmented photothermal conversion efficiency and enhanced colloidal stability in comparison with uncoated PDA shell AuNPs. The i-motif DNA nanostructure was assembled on PDA-coated AuNPs, which could be transformed into a C-quadruplex structure under an acidic environment, showing a characteristic pH response. The PDA shell served as a linker between the AuNPs and the i-motif DNA nanostructure. To enhance the specific cellular uptake, the AS1411 aptamer was introduced to the DNA nanostructure employed as a targeting ligand. In addition, Dox-loaded NPs (DAu@PDA-AS141) showed the pH/photothermal-responsive release of Dox. The photothermal effect of DAu@PDA-AS141 elicited excellent photothermal performance and efficient cancer cell inhibition under 808 nm near-infrared (NIR) irradiation. Overall, these results demonstrate that the DAu@PDA-AS141 nanoplatform shows great potential in synergistic photothermal-chemotherapy.

Lipid Nanoparticle Delivery System for mRNA Encoding B7H3-redirected Bispecific Antibody Displays Potent Antitumor Effects on Malignant Tumors.

The therapeutic use of bispecific T-cell engaging (BiTE) antibodies has shown great potential for treating malignancies. BiTE can simultaneously engage CD3ε on T cells and tumor antigen on cancer cells, thus exerting an effective antitumor effect. Nevertheless, challenges in production, manufacturing, and short serum half-life of BiTE have dampened some of the promise and impeded the pace of BiTE-based therapeutics to combat diseases. Nowadays, in vitro-transcribed mRNA has achieved programmed production, which is more flexible and cost-effective than the traditional method of producing recombinant antibody. Here, the authors have developed a BiTE-based mRNA treatment by encapsulating mRNA encoding B7H3×CD3 BiTE into a novel ionizable lipid nanoparticles (LNPs). The authors have found that LNPs have high transfection efficiency, and the hepatosplenic targeting capability of produce high concentrations of BiTE. Above all, a single intravenous injection of BiTE mRNA-LNPs could achieve high levels of protein expression in vivo and significantly prolonged the half-life of the BiTE, which can elicit robust and durable antitumor efficacy against hematologic malignancies and melanoma. Therefore, their results suggested that the therapeutic strategy based on mRNA expression of B7H3×CD3 BiTE is of potential research value and has promising clinical application prospects.

MADS-Box Protein Complex VvAG2, VvSEP3 and VvAGL11 Regulates the Formation of Ovules in Vitis vinifera L. cv. 'Xiangfei'.

The phenomenon of multi-carpel and multi-ovule exists in the grapevine cultivar 'Xiangfei', but the mechanism of ovule formation is seldom reported. In this study, we observed the ovule formation process by using 'Xiangfei' grapes. The role of the VvAG2 (VvAGAMOUS) gene in ovule formation was identified, and we explored the relationship between VvAG2, VvSEP3(VvMADS4) and VvAGL11(VvMADS5) proteins. The results showed that the ovule primordium appeared when the inflorescence length of 'Xiangfei' grapes were 4-5 cm long; the relative expression levels of VvAG2, VvAGL11 and VvSEP3 genes were higher during ovule formation, and the expression levels of VvAG2 gene was the highest. Transgenic tomato (Solanum lycopersicum) plants expressing VvAG2 produced higher numbers of ovules and carpels than the wild type. Moreover, yeast two-hybrid and yeast three-hybrid experiments demonstrated that VvSEP3 acts as a bridge and interacts with VvAG2 and VvAGL11 proteins, respectively. Meanwhile, a homodimer can be formed between VvSEP3 and VvSEP3, but there was no interaction between VvAG2 and VvAGL11. These findings suggest that the VvAG2 gene is involved in the formation of ovules, and VvAG2/VvSEP3 together with VvAGL11/VvSEP3 can form a tetrameric complex. In summary, our data showed that VvAG2 along with VvSEP3 and VvAGL11 jointly regulate the ovule formation of 'Xiangfei' grapes.

Stereocomplexed electrospun nanofibers containing poly (lactic acid) modified quaternized chitosan for wound healing.

Skin damage, especially the extensive full-thickness wound, is seriously affecting people's daily life and health. Meanwhile, wound healing is always challenged by bacterial infection. In this study, for the purpose of developing a disinfectant wound dressing, we designed a novel multi-functional nanofiber mats via electrospinning combining chitosan derivations and stereocomplex crystallite (SC). The SC membrane of poly (lactic acid)/chitosan derivatives were prepared via warming at 80 °C for 1 h. The thermal and mechanical properties of the heated mats were strengthened owing to the formation of SC, which restricted the lactide chains mobility. In vivo wound healing test revealed that the SC mats have better wound repair ability than the control group with a wound healing rate of 100 % within 15 days. In a word, the biomass-based mats with enhanced thermal and mechanical properties, antibacterial effect and antioxidant activity, providing a potential multi-functional platform for designing of disinfectant wound dressings.

Recent Perspectives in Hot Melt Extrusion-Based Polymeric Formulations for Drug Delivery: Applications and Innovations.

Hot melt extrusion (HME), a technology which mixing the advantages of solid dispersion technology and mechanical preparation, is accepted in varied applications in pharmaceutical formulations. When combined with other techniques, such as nanotechnique, three-dimensional printing, and co-extrusion, HME becomes much more multifunctional in the application of drug delivery. While in most cases, polymers employed in HME are responsible for the final property of products. The process of HME together with the selection of materials employed in HME were described briefly. In addition, the applications of HME in drug delivery and its currently status in the pharmaceutical field were also included. Some commercial products produced by HME have met the approval of FDA, indicating the commercial viability of this technique. Although showing great potential in pharmaceutical manufacturing, HME is still challenged by high temperature, shear force, and high input energy. Development of equipment, modifying the parameters, and optimization of polymeric formulations are needed for a safe, effective, and multifunctional hot melt extrusion drug delivery system. Also, wider range of combinations between HME and other techniques may provide guideline for developing multiple applications in drug delivery.

Strengthened and Thermally Resistant Poly(lactic acid)-Based Composite Nanofibers Prepared via Easy Stereocomplexation with Antibacterial Effects.

Strengthened poly(lactic acid) (PLA)-based materials with improved mechanical performance and improved thermal resistance, notably, are prepared by introducing stereocomplex crystallite (SC), an ideal filler, into the materials. Owing to the intermolecular hydrogen bond among the stereoisomer chains, the melting point of the special crystallite is up to 200 °C, which is 50 °C higher than the isostatic crystallite. The modulus of the PLA-based materials can be enhanced to several 100 MPa because of the integrated polymer chain arrangement. In this study, we electrospun hybrid nanofibers consisted of PLA stereoisomers and induced the stereocomplex crystallization under a mild condition (65 °C for 1 h). The mild warming is favorable for the protection of chlorogenic acid (CA) that was selected as the antibacterial agent. Both of Gram-positive and Gram-negative bacteria were efficiently cleared away using the warmed nanofibers that released CA rapidly within just a few hours. Used as filters, the SC electrospinning membrane also presented a potent filtering effect, leaving no bacteria retained in the filtrates. Attributing to SC, the PLA-based nanofibers showed extremely increased melting temperature over 200 °C and improved Young's modulus up to 270.0 MPa. The durable nanofibers prepared in present study are meaningful for enlarging the application of PLA-based materials, for example, as filters, masks, and packages.