Extracellular matrix-degrading STING nanoagonists for mild NIR-II photothermal-augmented chemodynamic-immunotherapy

Regulation of stimulator of interferon genes (STING) pathway using agonists can boost antitumor immunity for cancer treatment, while the rapid plasma clearance, limited membrane permeability, and inefficient cytosolic transport of STING agonists greatly compromise their therapeutic efficacy. In this study, we describe an extracellular matrix (ECM)-degrading nanoagonist (dNAc) with second near-infrared (NIR-II) light controlled activation of intracellular STING pathway for mild photothermal-augmented chemodynamic-immunotherapy of breast cancer. The dNAc consists of a thermal-responsive liposome inside loading with ferrous sulfide (FeS2) nanoparticles as both NIR-II photothermal converters and Fenton catalysts, 2′3′-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) as the STING agonist, and an ECM-degrading enzyme (bromelain) on the liposome surface. Mild heat generated by dNAc upon NIR-II photoirradiation improves Fenton reaction efficacy to kill tumor cells and cause immunogenic cell death (ICD). Meanwhile, the generated heat triggers a controlled release of cGAMP from thermal-responsive liposomes to active STING pathway. The mild photothermal activation of STING pathway combined with ICD promotes anti-tumor immune responses, which leads to improved infiltration of effector T cells into tumor tissues after bromelain-mediated ECM degradation. As a result, after treatment with dNAc upon NIR-II photoactivation, both primary and distant tumors in a murine mouse model are inhibited and the liver and lung metastasis are effectively suppressed. This work presents a photoactivatable system for STING pathway and combinational immunotherapy with improved therapeutic outcome. Graphical Abstract

Antiviral Effects of Gelatin Stabilized Ferrous Sulfide Nanoparticles

Ferrous sulfide nanoparticles (FeS NPs) are widely applied to environmental remediation, catalysis, energy storage and medicine because of their high reactivity, large specific surface area and low cost, arousing great interest of researchers. However, there is no literature reported on its application in the antiviral field. In the study, gelatin stabilized FeS nanoparticles (Gel-FeS NPs) were synthesized by co-precipitation of Fe2+ and S2‒ in the aqueous phase with continuous stirring under anaerobic conditions. The as-prepared Gel-FeS NPs were good stabilization and dispersibility with the size distribution of 77.7 ± 16.4 nm, as determined by UV-Vis spectrometer, TEM, FTIR, XRD and XPS. We reported for the first time the virucidic and antiviral activity of Gel-FeS NPs. The Gel-FeS NPs with good dispersibility and biocompatibility were synthesized, and they exhibited effective inhibition on the proliferation of PRRSV by blocking the PRRSV outside the host cells. Moreover, the Fe2+ from degraded ferrous sulfide still displayed an antiviral effect, demonstrating the advantage as an antiviral nanomaterial of Gel-FeS NPs compared to other nanomaterials. This work highlighted the antiviral effect of Gel-FeS NPs, broaden the applications of iron-based nanoparticles for combating the virus.

Enhanced Nitrogen and Phosphorus Removal by Natural Pyrite based Constructed Wetland with Intermittent Aeration

Four subsurface flow constructed wetlands (SFCWs) filled with different substrates including ceramsite, ceramsite + pyrite, ceramsite + ferrous sulfide, and ceramsite + pyrite + ferrous sulfide (labeled as SFCW-S1, SFCW-S2, SFCW-S3, and SFCW-S4) were constructed, and the removal of nitrogen and phosphorus by these SFCWs coupled with intermittent aeration in the front section was discussed. The key findings from different substrate analyses, including nitrification and denitrification rate, enzyme activity, microbial community structure, and the X-ray diffraction, revealed the nitrogen and phosphorus removal mechanism. The results showed that the nitrogen and phosphorus removal efficiency for SFCW-S1 always remains the lowest, and the phosphorus removal efficiency for SFCW-S4 is recorded as the highest one. However, after controlling the dissolved oxygen by intermittent aeration in the front section of SFCWs, the nitrogen and phosphorus removal efficiencies of SFCWs-S2 and S4 becomes higher than those of SFCW-S1, and SFCW-S3. It was noticed that the pollutants were removed mainly in the front section of the SFCWs. Both precipitation and adsorption on the substrate were the main mechanisms for phosphorus removal. A minute difference of nitrification rate and ammonia monooxygenase activity was observed in the SFCWs aeration zone. The denitrification rates, nitrate reductase, nitrite reductase, and electron transport system activity for SFCW-S2 and SFCW-S4 were higher than those detected for SFCW-S1 and SFCW-S3 in the non-aerated zone. Proteobacteria was the largest phyla found in the SFCWs. Moreover, Thiobacillus occupied a large proportion found in SFCW-S2, and SFCW-S4, and it played a crucial role in pyrite-driven autotrophic denitrification.