Synergistic strategy with hyperthermia therapy based immunotherapy and engineered exosomes−liposomes targeted chemotherapy prevents tumor recurrence and metastasis in advanced breast cancer

Advanced breast cancer with recurrent and distal organ metastasis is aggressive and incurable. The current existing treatment strategies for advanced breast cancer are difficult to achieve synergistic treatment of recurrent tumors and distant metastasis, resulting in poor clinical outcomes. Herein, a synergistic therapy strategy composed of biomimetic tumor-derived exosomes (TEX)-Liposome-paclitaxel (PTX) with lung homing properties and gold nanorods (GNR)-PEG, was designed, respectively. GNR-PEG, with well biocompatibility, cured recurrent tumors effectively by thermal ablation under the in situ NIR irradiation. Meanwhile, GNR-mediated thermal ablation activated the adaptive antitumor immune response, significantly increased the level of CD8+ T cells in lungs and the concentration of serum cytokines (tumor necrosis factor-α, interlekin-6, and interferon-γ). Subsequently, TEX-Liposome-PTX preferentially accumulated in lung tissues due to autologous tumor-derived TEX with inherent specific affinity to lung, resulting in a better therapeutic effect on lung metastasis tumors with the assistance of adaptive immunotherapy triggered by GNR in vivo. The enhanced therapeutic efficacy in advanced breast cancer was a combination of thermal ablation, adaptive antitumor immunotherapy, and targeted PTX chemotherapy. Hence, the synergistic strategy based on GNR and TEX-Liposome provides selectivity to clinical treatment of advanced breast cancer with recurrent and metastasis

Gold Nanoclusters Potentially Facilitate Dentin Regeneration by Functioning Immunomodulation

It is presently difficult to achieve dental pulp vitality maintenance and regeneration in adult teeth. Dentin destruction results in the exposure of the dental pulp tissue to infectious oral environments, thereby triggering continuous severe pulp inflammation that impedes the self-regenerative capacity of the pulp. For these reasons, the regeneration of dentin bridges to block pulp tissue from the oral environment is an indispensable step. Nevertheless, this goal is difficult to achieve using present strategies, because the importance of immunoregulation in the pulp inflammatory microenvironment has been ignored. In our previous study, we found that the nanomaterial dihydrolipoic acid-functionalized gold nanoclusters (DHLA-AuNCs) efficiently regulated inflammatory responses in microglia (resident macrophages in the central nervous system), suggesting that DHLA-AuNCs may induce dentin bridge regeneration by regulating dental pulp macrophage responses. In the present study, we found that DHLA-AuNCs inhibited the M1 phenotype while promoting the M2 phenotype in macrophages in inflammatory conditions in vitro. This regulation of the inflammatory environment in dental pulp enhanced the differentiation of human dental pulp stromal cells (hDPC) toward odontoblasts, a beneficial effect on dentin regeneration. DHLA-AuNCs also had a direct role in the differentiation and mineralization of hDPC. These findings suggest that DHLA-AuNCs facilitate dentin regeneration through both efficient immunomodulation and direct induction of stromal cell differentiation/mineralization, providing a potential therapeutic nanomaterial for dentin bridge regeneration, effects that would be beneficial for dental pulp regeneration.</p

Preparation of Antibacterial Cellulose Paper Using Layer-by-Layer Assembly for Cooked Beef Preservation at Ambient Temperature

Positively-charged ε-poly(l-lysine) (ε-PL) and negatively-charged carboxymethyl cellulose (CMC) were alternately deposited on a cellulose paper surface by the layer-by-layer (LBL) assembly technique. The formation of ε-PL/CMC multilayers was confirmed by X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectra (FTIR), and zeta potential measurement. The morphologies of the multilayer-modified cellulose paper were observed by scanning electron microscopy (SEM). The ε-PL/CMC multilayers effectively improved not only the antibacterial activity of cellulose paper against both Escherichia coli and Staphylococcus aureus, but also the cellulose paper tensile strength property. Cellulose paper modified with a (ε-PL/CMC)4.5 multilayer exhibited the strongest antibacterial activity, selected for preserving cooked beef for nine days at ambient temperature, could extend the shelf-life of beef for about three days compared with common commercial PE films. The prepared antibacterial paper did not show any evidence of the cytotoxic effect since it could not increase the cytoplasmic lactate dehydrogenase release from L-929 fibroblast cells in contact with the antibacterial paper, suggesting the possibility of utilization in food packaging field

Effects of PLA Film Incorporated with ZnO Nanoparticle on the Quality Attributes of Fresh-Cut Apple

A novel nanopackaging film was synthesized by incorporating ZnO nanoparticles into a poly-lactic acid (PLA) matrix, and its effect on the quality of fresh-cut apple during the period of preservation was investigated at 4 ± 1 °C for 14 days. Six wt % cinnamaldehyde was added into the nano-blend film. Scanning electron microscope (SEM) analysis showed a rougher cross-section of the nano-blend films and an X-ray diffraction (XRD) was carried out to determine the structure of the ZnO nanoparticles. Compared to the pure PLA film, the nano-blend film had a higher water vapor permeability (WVP) and lower oxygen permeability. With the increase of the nanoparticles (NPs) in the PLA, the elongation at break (ε) and elastic modulus (EM) increased, while tensile strength (TS) decreased. Thermogravimetric analysis (TGA) presented a relatively good thermostability. Most importantly, the physical and biochemical properties of the fresh-cut apple were also measured, such as weight loss, firmness, polyphenol oxidase (PPO), total phenolic content, browning index (BI), sensory quality, and microbiological level. The results indicated that nano-blend packaging films had the highest weight loss at the end of storage compared to the pure PLA film; however, nanopackaging provided a better retention of firmness, total phenolic countent, color, and sensory quality. It also had a remarkable inhibition on the growth of microorganisms. Therefore, Nano-ZnO active packaging could be used to improve the shelf-life of fresh-cut produce

Effect of high antioxidant activity on bacteriostasis of lignin from sugarcane bagasse

Lignin is widely used as an alternative to fossil resources in industrial production. However, its applications are limited due to its wide molecular weight distribution and chemical heterogeneity. In this study, alkali treated lignin (KL) and dilute acid-alkali treated lignin (DAKL) were prepared and compared through analyzing the functional groups, antioxidant and antibacterial activity of lignin. The results showed that DAKL displayed a smaller weight-average molecular weight (756 g/mol) and higher purity (93.74%). Further results showed that high contents of phenolic, syringyl (S), and guaiacyl (G) in DAKL increased its antioxidant activity (IC50: 38.5 mu g/ mL). Furthermore, DAKL exhibited a more excellent antibacterial effect on Staphylococcus aureus (96.71%) and Escherichia coli (100%) due to (1) the presence of several phenolic substances in lignin that damaged and ruptured the bacterial cell membrane, causing leakage of cell contents and bacterial death and (2) small molecule weight of lignin that allow it to penetrate the bacterial cell membrane, changing the physiological conditions of bacterial cell fluid and leading to cell death

Effect of supramolecular structural changes during the crystalline transformation of cellulose on its enzymatic hydrolysis

Currently, the main problems in cellulose conversion to glucose are the low enzymatic hydrolysis efficiency and the high cellulase cost. In this study, cellulose I allomorph substrates were from p-toluenesulfonic acid (PT), dilute sulfuric acid (DA) and sulfite (SP) treated cellulose substrates, and cellulose II allomorph were prepared by mercerization. XRD, NMR, FTIR and molecular docking were used to investigate the effect of cellulose allomorphs on hydrolysis efficiency. The results showed that cellulose II allomorph had a lower cellulase adsorption capacity and higher hydrolysis efficiency. This was because cellulose II allomorph owned gt conformation, and less tg and gg conformations of C-6 hydroxymethyl, causing the reduction of interchain hydrogen bonds and the increase in hydrolysis efficiency (PT, DA and SP: from 62.04%, 65.62% and 63.21% to 83.23%, 89.24% and 87.65%, respectively). This study provided theoretical supports for further understanding the effect of cellulose allomorphs on enzymatic hydrolysis

Development of Antimicrobial Packaging Film Made from Poly(Lactic Acid) Incorporating Titanium Dioxide and Silver Nanoparticles

Polylactide (PLA)/nano-TiO2 and PLA/nano-TiO2/nano-Ag blends films were prepared by a solvent volatilization method. Compared to pure PLA film, the nano-blend films have low water vapor permeability (WVP) and a poor transparency. With the increase of the NPs in the PLA, the tensile strength (TS) and elastic modulus (EM) decreased, while the elongation at break (ε) increased. SEM analysis indicated a rougher cross-section of the nano-blend films. According to the FTIR analysis, no new chemical bonds were formed in the nano-blend films. By using DSC to examine the crystallization and melting behavior, the result shows that the NPs have no effect on the glass transition (Tg) and melting temperature (Tm), but they caused an increase on the cold crystallization (Tc) and crystallinity (Xc). TGA results show that the addition of nanoparticles significantly improved the thermal stability. The PLA nano-blend films show a good antimicrobial activity against. E. coli and Listeria monocytogenes. Most important, we carried out migration tests, and verified that the release of NPs from the nano-blend films was within the standard limits

Dihydrolipoic acid-gold nanoclusters regulate microglial polarization and have the potential to alter neurogenesis

Microglia-mediated neuroinflammation is one of the most significant featuresin a variety of central nervous system (CNS) disorders such as traumatic brain injury, stroke,and many neurodegenerative diseases. Microglia become polarized upon stimulation. Thetwo extremes of the polarization are the neuron-destructive proinflammatory M1-like andthe neuron-regenerative M2-like phenotypes. Thus, manipulating microglial polarizationtoward the M2 phenotype is a promising therapeutic approach for CNS repair andregeneration. It has been reported that nanoparticles are potential tools for regulatingmicroglial polarization. Gold nanoclusters (AuNCs) could penetrate the blood−brain barrierand have neuroprotective effects, suggesting the possibility of utilizing AuNCs to regulatemicroglial polarization and improve neuronal regeneration in CNS. In the current study,AuNCs functionalized with dihydrolipoic acid (DHLA−AuNCs), an antioxidant withdemonstrated neuroprotective roles, were prepared, and their effects on polarization of amicroglial cell line (BV2) were examined. DHLA−AuNCs effectively suppressedproinflammatory processes in BV2 cells by inducing polarization toward the M2-likephenotype. This was associated with a decrease in reactive oxygen species and reduced NF-kB signaling and an improvement incell survival coupled with enhanced autophagy and inhibited apoptosis. Conditioned medium from DHLA−AuNC-treated BV2cells was able to enhance neurogenesis in both the neuronal cell line N2a and in an ex vivo brain slice stroke model. The directtreatment of brain slices with DHLA−AuNCs also ameliorated stroke-related tissue injury and reduced astrocyte activation(astrogliosis). This study suggests that by regulating neuroinflammation to improve neuronal regeneration, DHLA−AuNCscould be a potential therapeutic agent in CNS disorders