Immunoactivity of a hybrid membrane biosurface on nanoparticles: enhancing interactions with dendritic cells to augment anti-tumor immune responses.

Nano-biointerfaces play a pivotal role in determining the functionality of engineered therapeutic nanoparticles, particularly in the context of designing nanovaccines to effectively activate immune cells for cancer immunotherapy. Unlike involving chemical reactions by conventional surface decorating strategies, cell membrane-coating technology offers a straightforward approach to endow nanoparticles with natural biosurfaces, enabling them to mimic and integrate into the intricate biosystems of the body to interact with specific cells under physiological conditions. In this study, cell membranes, in a hybrid formulation, derived from cancer and activated macrophage cells were found to enhance the interaction of nanoparticles (HMP) with dendritic cells (DCs) and T cells among the mixed immune cells from lymph nodes (LNs), which could be leveraged in the development of nanovaccines for anti-tumor therapy. After loading with an adjuvant (R837), the nanoparticles coated with a hybrid membrane (HMPR) demonstrated effectiveness in priming DCs both in vitro and in vivo, resulting in amplified anti-tumor immune responses compared to those of nanoparticles coated with a single type of membrane or those lacking a membrane coating. The elevated immunoactivity of nanoparticles achieved by incorporating a hybrid membrane biosurface provides us a more profound comprehension of the nano-immune interaction, which may significantly benefit the development of bioactive nanomaterials for advanced therapy.

Insight into dissolved organic nitrogen transformation and characteristics: Focus on printing and dyeing wastewater treatment process.

Textile industry discharges large amounts of printing and dyeing wastewater (PDW) containing high concentration of refractory dissolved organic nitrogen (DON). However, the DON transformation and characteristics during PDW treatment, and its potential environment impact receive little concern. Treatment groups of dyeing wastewater (G-RB5), printing wastewater (G-Urea) and domestic wastewater (G-NH4Cl) with Reactive Black 5 (RB5), Urea and NH4Cl as influent nitrogen species were set to compare the DON behavior during the hydrolytic acidification-aerobic-anoxic process. G-RB5 exhibited higher DON concentrations with greater fluctuations, and its effluent dominated low molecular weight (LMW) and hydrophilic DON, showing high bioavailability (67.6%) and low biodegradation (8.0%). In the aerobic section, the concentration of microorganism-derived DON in G-RB5 was higher but the nitrogen species were fewer than G-Urea and G-NH4Cl. Grey relational analysis revealed that Proteobacteria and Thauera were the common bacteria strains showing high association degree (γ > 0.9) with biodegradable DON (ABDON) in all groups; while microbes related with biodegradable DON (BDON) varied between groups. The higher contents of DON, ABDON, LMW-DON and hydrophilic DON induced by RB5 highlight the importance of controlling DON from textile industry to mitigate the potential risk like algae growth stimulation, which needs more attention in future.

Iron scraps packing rapidly enhances nitrogen removal in an aerobic sludge system and the mechanism.

Simultaneous nitrification and denitrification (SND) has the advantage of energy saving and carbon demand reduction. Here, readily available low-cost iron scraps packing was added to an aerobic sludge system. This successfully enhanced the efficiency of total nitrogen removal from 37.7 ± 13.2 % to 62.7 ± 7.9 % over 2 days. While electrons from iron biocorrosion did not contribute to nitrate reduction, iron promoted heterotrophic denitrification. The iron scraps changed the spatial distribution of the microbial community, where more denitrification bacteria accumulated around the packing and higher denitrification capacity was noted. Metagenomic analysis of the sludge cultured in the presence of iron scraps for 2 days revealed that, with the exception of the enriched amoA/B/C gene expression, the abundance of other key nitrogen removal genes showed little variation. Furthermore, the structure of the microbial community was unchanged probably due to the relatively short culturing period. However, metatranscriptomic analysis indicated that iron increased the abundance of nitrifying bacteria (i.e. unclassified Nitrosomonas, Nitrosomonas sp. Is79A3 and Nitrospira defluvii) and promoted higher expression of nitrification genes. Notably, iron scraps packing decreased the abundance of the key denitrification bacteria Thauera sp. MZ1T from 52.92 to 7.58 %. The expression of napA/B also decreased, while expression of narG/H/I increased by 9 to 23 fold and a 2 to 3 fold over expression was noted for nirS, norB/C and nosZ in the presence of iron scraps. This suggested that aerobic denitrification was inhibited and anaerobic denitrification was promoted. This study has provided in-depth understanding of the influence of iron on SND to improve the application of iron-supported biological processes.

A Macrophage Membrane-Polymer Hybrid Biomimetic Nanoplatform for Therapeutic Delivery of Somatostatin Peptide to Chronic Pancreatitis.

The clinical translation of therapeutic peptides is generally challenged by multiple issues involving absorption, distribution, metabolism and excretion. In this study, a macrophage membrane-coated poly(lactic-co-glycolic acid) (PLGA) nanodelivery system was developed to enhance the bioavailability of the somatostatin (SST) peptide, which faces the hurdles of short half-life and potential side effects in the treatment of chronic pancreatitis. Using a facile nanoprecipitation strategy, SST was loaded in the nanoparticles with an encapsulation efficiency (EE) and a loading efficiency (LE) of 73.68 ± 3.56% and 1.47 ± 0.07%, respectively. The final formulation of SST-loaded nanoparticles with the camouflage of macrophage membrane (MP-SST) showed a mean diameter of 151 ± 4 nm and an average zeta potential of −29.6 ± 0.3 mV, which were stable long term during storage. With an above 90% cell viability, a hemolysis level of about 2% (<5%) and a preference for being ingested by activated endothelial cells compared to macrophages, the membrane−polymer hybrid nanoparticle showed biocompatibility and targeting capability in vitro. After being intravenously administered to mice with chronic pancreatitis, the MP-SST increased the content of SST in the serum (123.6 ± 13.6 pg/mL) and pancreas (1144.9 ± 206.2 pg/g) compared to the treatment of (Dulbecco's phosphate-buffered saline) DPBS (61.7 ± 6.0 pg/mL in serum and 740.2 ± 172.4 pg/g in the pancreas). The recovery of SST by MP-SST downregulated the expressions of chronic pancreatitis-related factors and alleviated the histologic severity of the pancreas to the greatest extent compared to other treatment groups. This augmentation of SST therapeutic effects demonstrated the superiority of integrating the synthetic polymer with biological membranes in the design of nanoplatforms for advanced and smart peptide delivery. Other peptides like SST can also be delivered via the membrane−polymer hybrid nanosystem for the treatment of diseases, broadening and promoting the potential clinical applications of peptides as therapeutics.

Quaternized carbon quantum dots with broad-spectrum antibacterial activity for the treatment of wounds infected with mixed bacteria.

Bacterial resistance to antibiotics have become one of the most severe threats in global public health, so the development of new-style antimicrobial agents is urgent. In this work, quaternized carbon quantum dots (qCQDs) with broad-spectrum antibacterial activity were synthesized by a simple green "one-pot" method using dimethyl diallyl ammonium chloride and glucose as reaction precursors. The qCQDs displayed satisfactory antibacterial activity against both Gram-positive and gram-negative bacteria. In rat models of wounds infected with mixed bacteria, qCQDs obviously restored the weight of rats, significantly reduced the death of rats from severe infection, and promoted the recovery and healing of infected wounds. Biosafety tests confirmed that qCQDs had no obvious toxic and side effects during the testing stage. The analysis of quantitative proteomics revealed that qCQDs mainly acted on ribosomal proteins in Staphylococcus aureus (Gram-positive bacteria) and significantly down-regulated proteins associated with citrate cycle in Escherichia coli (Gram-negative bacteria). Meanwhile, real-time quantitative PCR confirmed that the variation trend of genes corresponding to the proteins associated with ribosome and citrate cycle was consistent with the proteomic results after treatment of qCQDs, suggesting that qCQDs has a new antibacterial mechanism which is different from the reported carbon quantum dots with antibacterial action. STATEMENT OF SIGNIFICANCE: With the development of the research on carbon quantum dots, the application of carbon quantum dots in the field of medicine has attracted extensive attention. In this paper, quaternized carbon quantum dots (qCQDs) with antimicrobial activity prepared by specific methods were studied, including antimicrobial spectrum, antimicrobial mechanism and in vivo antimicrobial application. The antimicrobial mechanism of qCQDs was studied by proteomics and RT-qRCR, and the different mechanisms of qCQDs against Gram-positive and Gram-negative bacteria were also found. This study provides a research foundation for the application of carbon quantum dots in antimicrobial field, and also expands the application range of carbon quantum dots in medicine field.

Non-Viral Gene Delivery Systems for Treatment of Myocardial Infarction: Targeting Strategies and Cardiac Cell Modulation.

Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality worldwide. Conventional therapies involving surgery or pharmacological strategies have shown limited therapeutic effects due to a lack of cardiac tissue repair. Gene therapy has opened an avenue for the treatment of cardiac diseases through manipulating the underlying gene mechanics. Several gene therapies for cardiac diseases have been assessed in clinical trials, while the clinical translation greatly depends on the delivery technologies. Non-viral vectors are attracting much attention due to their safety and facile production compared to viral vectors. In this review, we discuss the recent progress of non-viral gene therapies for the treatment of cardiovascular diseases, with a particular focus on myocardial infarction (MI). Through a summary of delivery strategies with which to target cardiac tissue and different cardiac cells for MI treatment, this review aims to inspire new insights into the design/exploitation of non-viral delivery systems for gene cargos to promote cardiac repair/regeneration.

Endothelial cell membrane-based biosurface for targeted delivery to acute injury: analysis of leukocyte-mediated nanoparticle transportation.

Mimicking and leveraging biological structures and materials provide important approaches to develop functional vehicles for drug delivery. Taking advantage of the affinity and adhesion between the activated endothelial cells and innate immune cells during inflammatory responses, hybrid polyester nanoparticles coated with endothelial cell membranes (EM-P) containing adhesion molecules were fabricated and their capability as vehicles to travel to the acute injury sites through leukocyte-mediated processes was investigated. The in vivo studies and quantitative analyses performed through the lung-inflammation mouse models demonstrated that the EM-Ps preferentially interacted with the neutrophils and monocytes in the circulation and the cellular membrane-based biosurface improved the nanoparticle transportation to the inflamed lung possibly via the motility of neutrophils. Utilizing the transgenic zebrafish model, the leukocyte-mediated transportation and biodistribution of EM-Ps were further visualized in real time at the whole-organism level. Endothelial membranes provided a new biosurface for developing biomimetic vehicles to allow the immune cell-mediated transportation and may enable advanced systems for active and highly efficient drug delivery.

The PLGA nanoparticles for sustainable release of CGRP to ameliorate the inflammatory and vascular disorders in the lung of CGRP-deficient rats.

The calcitonin gene-related peptide (CGRP) has been demonstrated relating to vascular and inflammatory regulations not only the nerve systems. As the anti-inflammation factor and the most potent vasodilator, the CGRP holds therapeutic potentials for the treatment of cardiovascular diseases which was, however, limited by its peptide nature and short half-life. With advantages in improving the stability, circulation time and protection from degradation, the nanoparticles were promising as delivery carriers for the peptide. Nevertheless, few nanoparticulate systems were developed to deliver the CGRP peptide for the modulation of vascular or inflammatory functions instead of neural regulation. In this study, the CGRP was encapsulated into the poly (lactic-co-glycolic acid) (PLGA) nanoparticle for sustained release of CGRP in vivo. The nanoparticles recovered the systemic level of CGRP and the vascular inflammatory factors in the CGRP+/- rats comparing to the administration of (Dulbecco's Phosphate Buffered Saline) DPBS or peptide only. With the decrease of vascular wall thickness and the attenuation of the T cell infiltration in the lung, the polymer based CGRP delivery system showed potentials to facilitate the therapeutic effects of the CGRP which may help for the development of CGRP-based therapy in vascular and inflammatory disorder related diseases.