Hydroxyl Radical Formation Research Articles

Hydroxylated-Benz[a]anthracenes Induce Two Apoptosis-Related Gene Expressions in the Liver of the Nibbler Fish Girella punctata

Polycyclic aromatic hydrocarbons (PAHs) are known to have toxic effects on fish. In this study, we examined the effects of benz[a]anthracene (BaA), a type of PAH, on fish liver metabolism. Nibbler fish (Girella punctata) were intraperitoneally injected with BaA (10 ng/g body weight) four times over a 10-day period. BaA significantly decreased known bone metabolism-related plasma factors such as calcium and inorganic phosphorus. Moreover, significant reductions were observed in the plasma levels of known liver metabolism-related factors, including ferrous ions, total bile acids, total bilirubin, free bilirubin, aspartate aminotransferase, and alkaline phosphatase. Interestingly, mono-hydroxylated metabolites of BaA, such as 3 hydroxylbenz[a]anthracene (3-OHBaA), were detected in the bile of BaA-injected nibbler fish. This hydroxylated form of BaA was found in its free form, rather than conjugated with glucuronic acid or sulfuric acid. Due to the lack of whole-genome sequence data for the nibbler fish, two nibbler fish-specific apoptosis-related factors (TNF receptor superfamily member 1A: tnfrsf1a and TNF superfamily member 10: tnfsf10) were isolated by De novo RNA sequencing. In a liver tissue culture, 3-OHBaA (10−6 M) significantly upregulated the expression of tnfrsf1a and tnfsf10 in the liver. These results provide the first evidence that 3-OHBaA metabolites exhibit toxic effects on the liver in teleost.

Oxidation Triggered Supramolecular Chirality.

Topochemical reactions normally occurring in the solid and crystalline state exhibit solvent-free and catalyst-free properties, with high atom economy properties, which have been widely applied in materials science and polymer synthesis. Herein, we explore the potential of topochemical reactions for controlling the emergence of supramolecular chirality and the precise fabrication of chiroptical materials. Boronic acid pinacol esters (BPin) were conjugated to naphthalimides containing an inherent chiral cholesteryl group linked by alkyl or benzene spacers. The BPin segments were oxidized by H2O2 to form hydroxyl groups, which enhanced luminescence, reduced steric effects, and increased amphiphilicity. The inherent liposomal aggregates underwent in situ oxidation and transformed into 1D nanoarchitectures, exhibiting macroscopic chirality, active Cotton effects, and circularly polarized luminescence. Oxidation could also initiate an intimate interplay between the building units and the guest molecule, by which the chirality and chiroptical evolution in the multiple component chiral assembly system were realized.

The performance and mechanism of friction-promoted two-electron fully water splitting of boron carbide

The decomposition of hydrogen peroxide is an essential intermediate step in the kinetically advantageous two electrons in the process of splitting water (2H2O =H2O2+H2,H2O2→12O2+H2O). Although it is an exothermic reaction, the reaction rate is slow without catalyst. It is possible to significantly improve the efficiency of water splitting if hydrogen peroxide can be decomposed in a timely and rapid manner. Hydrogen peroxide can be quickly decomposed by tribocatalysis process to solve the above problems. In the process of friction catalysis, when external force is applied to piezoelectric material B4C, internal charge separation will be generated and local electric field will be formed. Tribocatalysis can continuously generate rapidly separated electrons and positive charges, which provide sufficient electrons for the two-electron water splitting process. At the same time, under the tribocatalysis of boron carbide (B4C), water molecules are easily combined with positive charges to form hydroxyl radicals and release hydrogen ions. It provides a continuous source of hydrogen ions for the generation of hydrogen, which consumes positive charges and improves the utilization efficiency of electrons. Finally, two moles of hydroxyl radicals quickly form hydrogen peroxide, which is rapidly decomposed by tribocatalysis, thus solving the bottleneck problem of two-electron water splitting. Under tribocatalytic-driven, the dual function of B4C: catalytic water splitting and decomposition of hydrogen peroxide is the key to its efficient catalytic continuous production of hydrogen and oxygen.

Direct colorimetric detection of triacetone triperoxide explosive by hydroxylamine-mediated fenton chemistry catalyzed by goethite nanoparticles

Due to the absence of nitro groups or aromatic structures in its structure, spectrophotometric methods that can directly determine triacetone triperoxide (TATP) are absent. In the proposed study, a molecular spectroscopic sensor was developed based on the decomposition of TATP by hydrolysis without the addition of external acid, allowing the direct determination of TATP. The detection principle of the developed sensor is based on the decomposition of TATP by the hydrochloric acid formed as a result of the reaction of TATP with hydroxylamine hydrochloride, taking advantage of the solubility of TATP in acetone, and the hydrogen peroxide formed as a degradation product to form hydroxyl radicals catalyzed by goethite nanoparticles. The formed hydroxyl radicals, thanks to their strong oxidation properties, oxidized N,N-dimethyl-p-phenylenediamine (DMPD) to the pink-colored DMPD•+ radical cation, and the direct determination of TATP was performed by measuring the absorbance of the colored product formed. Thus, a chemo-cybernetic sequence of reactions is proposed for intact TATP assay in a circular self-sustained system, where the reactants at a given step of reactions are supplied by the products of a previous step. By applying the developed method to TATP samples prepared in acetone, absorbances due to DMPD•+ were read at 554 nm to evaluate the results. A calibration curve was created between absorbance versus TATP concentration within a final range of 10 – 33 mg L-1. The limit of detection (LOD) and limit of quantification (LOQ) of the developed TATP method were 3.3 mg L-1 and 10.8 mg L-1, respectively. Five replicate measurements were performed to determine the intra-assay and inter-assay precision of the spectrophotometric determination of TATP, and the relative standard deviations (RSD %) for TATP were found as 2.70 % and 3.76 %, respectively. Interference analysis was carried out to see the effects of ions commonly present in soil/groundwater, and of the substances used as camouflage materials due to their color and appearance similarity to TATP. The selectivity of the method toward TATP was investigated by examining the analyte recovery from explosive mixtures. The developed method was validated against a reference GC–MS method using TATP-contaminated soil samples, and the results were compared statistically.

Cu2O@Cu-composed hollow spheres capable of Generating Rich reactive oxygen species for efficient photodynamic antibacterial application

Cuprous oxide (Cu2O), which has an appropriate band gap, is widely used as a marine antifouling biocide. This makes it increasingly valuable for photocatalytic antibacterial applications. Using crystal engineering technology to create Cu2O with tailored Cu2O/Cu interfaces and crystal planes can effectively enhance its performance but presents challenges. Herein, we report a simple wet chemical method for the controlled preparation of Cu2O@Cu hollow heterostructure. Experimental results demonstrate that the prepared composites exhibited highly efficient and broad-spectrum photocatalytic antibacterial effects against both Gram-negative and Gram-positive bacteria, achieving 100% antibacterial efficiency under 10 min of irradiation, much more effective than the bulk Cu2O. Characterization results show that a hollow spherical structure consisted of fine Cu2O@Cu nanoparticles in their wall, and the generated interfaces facilitated the migration and separation of photogenerated charge carriers and promoted the formation of hydroxyl radicals with stronger oxidizing abilities. Meanwhile, the Cu outside layer of each Cu2O@Cu particle not only acted as a shield to protect Cu2O from corrosion but also served as an electron acceptor to efficiently transfer photogenerated electrons, thereby demonstrating highly effective and stable antibacterial performance. This study not only offers a valuable reference for developing highly efficient and universal photocatalytic materials but also provides insight into the chemical reaction in the photocatalytic antibacterial process.

Ozone-microbubble-enhanced oxidation of pharmaceuticals and personal care products in municipal secondary effluents

Microbubble aeration can greatly improve ozonation by enhancing ozone transfer and subsequent hydroxyl radical formation. Here, we applied microbubble ozonation to treat pharmaceuticals and personal care products (PPCPs) in several municipal secondary effluents. Compared with conventional ozonation, microbubble ozonation efficiently eliminated both ozone-reactive and ozone-resistant PPCPs and greatly reduced the ozone doses in the complex water matrixes of the secondary effluents. In addition, compared with millibubble ozonation, the removal of chemical oxygen demand (COD) increased by 32.0%–67.2% at 60mg/L ozone dose during microbubble ozonation. The carbon emission of microbubble ozonation varied in different water matrix, and was 47–76% less than that of millibubble ozonation. The oxidizing capacity ratio of microbubble to millibubble for PPCPs was between 1.26 to 3.50 times, and ozone-resistant PPCPs removal was enhanced more than ozone-reactive PPCPs by microbubble ozonation. Specifically, the oxidizing capacity ratio of microbubble to millibubble for carbamazepine (ozone-reactive) was 1.30 to 2.43 times, whereas that for N,N-diethyl-3-tolumide (ozone-resistant) was 1.88 to 3.50 times. Microbubble ozonation also greatly decreased the UV absorbance and fluorescence for all of the water samples. The UV absorbance at 254, 280, and 320nm decreased by 64.0%–83.8%, and the fluorescence peak intensity decreased by more than 94%. Surrogates for the removal of PPCPs and COD were evaluated and compared. This study provides new insights into the application of microbubble ozonation to control PPCPs in secondary effluents.

Theoretical research of the NO and N2O reduction by char in oxy-fuel CFBC: Influence of H2O

Oxy-fuel CFBC has lower NOx emissions compared to air combustion, with the high H2O content affecting NO and N2O reduction. This study, using density functional theory and transition state theory, investigates the impact of H2O on the char model at the electronic level and its subsequent influence on NO and N2O reduction. Results reveal that H2O adsorbs onto the active site on char, forming hydroxyl groups and free H atoms. The unstable O atom in –OH group leads to benzene ring rearrangement in the char model, creating additional active sites. NO reduction follows two paths: producing CO(R1) or CO2(R2). For N2O reduction(R3), N2O reduction precedes benzene ring cracking, with CO2 production providing more active sites. In R1, CO formation limits reactive sites and increases activation energy, while R2 and R3 favor CO2 formation. Reaction pathways leading to CO2 formation show lower activation energies and higher pre-exponential factors for N2 release.

In-situ oxidative polymerization of dopamine triggered by CuO2 in acidic condition and application in "turn-off" sensing.

Dopamine (DA) is a key neurotransmitter whose concentration affects various neurological disorders. Unlike previous methods that synthesize non-fluorescent polydopamine (NFL-PDA) under alkaline conditions, this study introduces a novel "turn-off" sensing method for DA using NFL-PDA synthesized through a unique reaction pathway. In our approach, CuO2 nanodots, created via a simple reduction method, catalyze the formation of hydroxyl radicals (•OH) in acidic conditions, triggering the oxidative polymerization of DA into NFL-PDA. The reaction between DA and CuO2 nanodots in acidic solution was examined to understand the process. UiO-66-NH2 was then used to test NFL-PDA's fluorescence quenching ability and to further investigate the DA determination mechanism. Results showed that fluorescence quenching was due to enhanced non-radiative energy transfer and Förster resonance energy transfer (FRET) between NFL-PDA and UiO-66-NH2. This led to the development of a simple "turn-off" fluorometric DA determination method with a linear range of 0.1-200μmol/L and a limit of detection (LOD) of 0.0575μmol/L. Although this method does not outperform existing NFL-PDA synthesis methods under alkaline conditions, it provides a new synthesis approach and application for sensing DA, contributing to the basic theory of chemical sensing. Additionally, DA determination in human serum samples was successfully achieved, with results consistent with high-performance liquid chromatography (HPLC).

Unraveling the Effects of Strain-Induced Defect Engineering on the Visible-Light-Driven Photodynamic Performance of Zn2SnO4 Nanoparticles Modified by Larger Barium Cations.

Waterborne infections caused by pathogenic microorganisms represent serious health risks for humans. Ternary zinc-tin oxide nanoparticles have great potential as a cost-effective, environmentally friendly, and efficient candidate for waterborne infections; however, their photocatalytic and antibacterial effects are quite limited due to insufficient visible light absorption and rapid electron-hole recombination. Herein, barium-doped zinc stannate (Ba@ZTO) nanoparticles were synthesized by the hydrothermal method and used for the first time not only as antibacterial agents to prevent the spread of the harmful bacteria S. aureus and E. coli but also as photocatalysts to degrade the organic pollutant rhodamine B. Unexpectedly, Ba2+ ions exhibited compressive stress behavior instead of the predicted tensile stress when inserted into the ZTO crystal lattice, playing an active role in increasing oxygen vacancies within the crystal lattice and in the formation of hydroxyl radicals in the bulk solution and hydrogen peroxide (H2O2) radicals, significantly improving the photocatalytic and antibacterial properties. Strain-induced defects created by the insertion of larger barium ions into the ZTO lattice promote the increase of shallow traps for boosting photocatalytic/disinfection properties while suppressing deep-level traps that encourage nonradiative recombination. In essence, defect and strain engineering opens a promising route to achieve high disinfection efficiency by inducing larger cation ions under visible light in oxide-based materials.

Highly Efficient Visible-Light Photocatalysts: Bi2O3@TiO2 Derived from Ti-MOFs for Eriochrome Black T Degradation: A Joint Experimental and Computational Study

Herein, we synthesized Ti-MOF through a solvothermal method and subsequently calcined it to form anatase TiO2. We further developed a Bi2O3@TiO2 mixed oxide using impregnation and calcination processes. These oxides showed significant photocatalytic activity for degrading Eriochrome Black T (EBT) dye under visible light irradiation. We characterized the prepared samples using various techniques, including XRD, XPS, FTIR, BET, SEM, EDX, TEM, and UV-DRS analyses. Our results indicated that TiO2 and 10%Bi2O3@TiO2 achieved 80% and 100% degradation of EBT dye solution (50 ppm) within 30 min in acidic medium with a 50 mg catalyst dose, respectively. The calcination of the Ti-MOF into TiO2 improved its sensitivity to visible light. The Bi2O3@TiO2 composite was also effective in degrading other organic pollutants, such as Congo Red (degradation ~99%), Malachite Green (degradation ~95%), Methylene Blue (degradation ~81%), and Safranine O (degradation ~69%). The impregnation of Bi2O3 increased the surface acidity of TiO2, enhancing its photocatalytic activity by promoting hydroxyl group formation through increased water adsorption. Additionally, 10%Bi2O3@TiO2 demonstrated excellent chemical stability and reusability, maintaining high degradation efficiency over four cycles. Density Functional Theory (DFT) and Time-Dependent DFT (TD-DFT) calculations were performed to understand the degradation mechanisms. UV-Vis absorption spectrum simulations suggested that the anionic HEB−2 (O24) or EB−3 forms of the EBT dye are likely to undergo degradation. This study highlights the potential of Bi2O3@TiO2 composites for effective photocatalytic applications in environmental remediation.

Strong and Environmental-Friendly Adhesive Glass Based on Chitin Nanoparticles

Chitin is a biopolymer that can be used as a candidate material for a strong and environmentally friendly glass adhesive. In the form of nanoparticles with needle-like morphology and attractive functional groups in the form of amide and hydroxyl, Chitin Nanoparticle (ChNP) shows a strong Van der Walls adhesive force against glass. In the study, ChNP was successfully isolated from crab shells from the sea of Lombok. The isolated ChNP has a characteristic size around 351 nm with -chitin conformation and needle-shaped morphology. Based on the results of shear strength testing, 0.42 mg of ChNP can withstand a load of 21 kg and the addition of Gum Arabic (GA) and Hen Egg White lysozyme (HEWL) in a ratio of 1: 1 to ChNP succeeded in increasing adhesion by 72%.

Unveiling the Critical Pathways of Hydroxyl Radical Formation in Breakpoint Chlorination: The Role of Trichloramine and Dichloramine Interactions.

Chlorination of ammonia or chloramine-containing waters induces breakpoint chlorination reactions, producing a hydroxyl radical (•OH), but enhances the formation of undesirable N-nitrosamines. The prevailing view attributes •OH formation to a nitrosyl intermediate derived from the hydrolysis of dichloramine, but this pathway is unlikely at neutral or acidic pH. This study reveals a novel mechanism where •OH is generated via interactions between trichloramine (NCl3) and dichloramine (NHCl2), which also form nitrosation agents. Our experiments demonstrated that the NCl3-NHCl2 interaction degrades micropollutants with kinetics 2-3 times faster than breakpoint chlorination. Using electron paramagnetic resonance, we detected •OH in the NCl3-NHCl2 reaction. Micropollutant removal was unimpaired under low dissolved oxygen (O2(aq)) conditions, aligning with negligible O2(aq) changes during the NCl3-NHCl2 reaction and suggesting O2(aq) does not participate in •OH formation. Using benzene as a probe in 18O-labeled H2O, we confirmed water contributes to the oxygen source of •OH in NCl3-NHCl2 interactions, through which parallel reactions occur, leading to the formation of one mole of •OH alongside 1.92 mol of N2. A kinetic model developed in this study accurately predicted •OH and N2 and demonstrated the NCl3-NHCl2 interaction as the primary pathway for •OH formation in breakpoint chlorination, providing new insights into breakpoint chemistry.

Formation of Both Free Hydroxyl Radicals and Surface Oxygen During Catalytic Ozonation by Single-Atom Iron: An Overlooked Pollutant-Dependent Oxidation Mechanism

Formation of Both Free Hydroxyl Radicals and Surface Oxygen During Catalytic Ozonation by Single-Atom Iron: An Overlooked Pollutant-Dependent Oxidation Mechanism

Are Hydroxyl Radicals Spontaneously Generated in Unactivated Water Droplets?

AbstractSpontaneous ionization/breakup of water at the surface of aqueous droplets has been reported with evidence ranging from formation of hydrogen peroxide and hydroxyl radicals, indicated by ions at m/z 36 attributed to OH⋅‐H3O+ or (H2O‐OH2)+⋅ as well as oxidation products of radical scavengers in mass spectra of water droplets formed by pneumatic nebulization. Here, aqueous droplets are formed both by nanoelectrospray, which produces highly charged nanodrops with initial diameters ~100 nm, and a vibrating mesh nebulizer, which produces 2–20 μm droplets that are initially less highly charged. The lifetimes of these droplets range from 10s of μs to 560 ms and the surface‐to‐volume ratios span ~100‐fold range. No ions at m/z 36 are detected with pure water, nor are significant oxidation products for the two radical scavengers that were previously reported to be formed in high abundance. These and other results indicate that prior conclusions about spontaneous hydroxyl radical formation in unactivated water droplets are not supported by the evidence and that water appears to be stable at droplet surfaces over a wide range of droplet size, charge and lifetime.

Efficient activation of peroxymonosulfate by 3D blocky sponge-supported spinel ferrite nanocomposites for convenient removal of aniline

Aniline, a toxic aromatic amine prevalent in printing and dyeing effluents, has garnered significant attention due to its potential risks to human health and the environment. In this study, 3D blocky melamine sponge-supported spinel ferrite nanocomposites (MFe2O4@MS) were synthesized to activate peroxymonosulfate (PMS) for the removal of aniline from printing and dyeing wastewater. The CoFe2O4@MS-PMS achieved complete removal of aniline within 10 min across a pH range of 5 to 11, significantly outperforming the CuFe2O4@MS-PMS and ZnFe2O4@MS-PMS systems. Electron paramagnetic resonance (EPR) and probe-based kinetic model experiments certified the formation of sulfate radicals (•SO4−), hydroxyl radicals (•OH), and singlet oxygen (1O2) during the process, where •SO4− was identified as the principal reactive species responsible for aniline degradation. The Langmuir-Hinshelwood model demonstrated that the melamine sponge framework significantly improved the dispersion and adsorption capabilities of MFe2O4 nanoparticles. This enhancement led to localized enrichment of aniline and PMS on the surface. Furthermore, the removal of aniline by CoFe2O4@MS-PMS performed satisfactorily in five-cycle experiments and in actual printing and dyeing wastewater. This research offers new insights into the design and synthesis of environmentally friendly and highly active PMS catalysts for aniline degradation in industrial wastewater.

Atmospheric propane (C3H8) column retrievals from ground-based FTIR observations in Xianghe, China

Abstract. Propane (C3H8) is an important trace gas in the atmosphere, as it is a proxy for oil and gas production and has a significant impact on atmospheric chemical reactions related to the hydroxyl radical and tropospheric ozone formation. In this study, solar direct absorption spectra near 2967 cm−1 recorded by a ground-based Fourier transform infrared spectrometer (FTIR) were applied to retrieve C3H8 total columns between June 2018 and July 2022 in Xianghe in north China. The systematic and random uncertainties of the C3H8 column retrieval are estimated to be 18.4 % and 18.1 %, respectively. The mean and standard deviation of the C3H8 columns derived from the FTIR spectra in Xianghe are 1.80 ± 0.81 (1σ) × 1015 molec. cm−2. Good correlations are found between C3H8 and other non-methane hydrocarbons, such as C2H6 (R=0.84) and C2H2 (R=0.79), as well as between C3H8 and CO (R=0.72). However, the correlation between C3H8 and CH4 is relatively weak (R=0.45). Moreover, the FTIR C3H8 measurements in Xianghe are also compared against MkIV measurements at several sites around the world. The new FTIR measurements in Xianghe provide us with insight into C3H8 column variations and the underlying processes in north China.

Infrared Spectroscopy of Lunar Core 73001: Upper Limit on Hydration in a Lunar Sample With No History of Exposure to Terrestrial Water Vapor

AbstractThe lunar surface exhibits an absorption band near 3 μm due to hydration, either water or hydroxyl. In most analyses, the band is variable at least in latitude and temperature. Hypotheses for the variability include infilling of the band by thermal emission, migration of molecular water along temperature gradients, and formation and destruction of metastable hydroxyl as solar wind hydrogen diffuses through lunar surface grains. The degree to which lunar soil exhibits an inherent hydration feature in the absence of environmental influences is an open question. The recent opening of Apollo core sample 73001 that was sealed in vacuum on the lunar surface and curated in dry nitrogen since its return from the Moon affords an opportunity to determine if lunar soil exhibits a spectral feature due to hydration isolated from the lunar environment. To that end, near the close of dissection of the core into samples for allocation to the lunar science community, we introduced an infrared spectrometer into the nitrogen purged curation cabinet and collected reflectance spectra of portions of the core between 2 and 4 μm. We found no evidence of absorption due to hydration to 1.1% band depth uncertainty. The measurements were relative to a diffuse aluminum standard, which itself could possibly absorb light at 3 μm due to a thin film of water; we estimate a possible negative bias of about 50 μg/g equivalent water absorption, leading to a final estimate of core water abundance of 50 μg/g ± 50 μg/g. This finding does not contradict prior estimates of lunar surface hydration as core sample 73001 is immature and may not have had sufficient opportunity to gather enough hydrogen from the solar wind or water from micrometeorites to form detectable hydration. After exposure of the core to laboratory atmosphere, a strong 3 μm absorption developed, equivalent to over 1,000 μg/g at a rate of about 5 μg/g per minute, illustrating the sensitivity of lunar materials to water contamination, and the effectiveness of curation of the sample.

Efficient activation of sodium percarbonate by hydroxylamine-enhanced zero-valent transition metals for the removal of AZO: performance, free radical generation and mechanism

Azoxystrobin (AZO) fungicides are novel organic pollutants which are stable in water environment. These pollutants can be degraded using low cost zero-valent metals (zero-valent iron (ZVI) and zero-valent copper (ZVC)) to activate sodium percarbonate (SPC), and the introduction of hydroxylamine (HA) can effectively improve the reaction efficiency of this system. According to the experimental results, HA significantly promoted the regeneration of Fe2+ and Cu+ in the decomposed solution of SPC, significantly accelerating the formation of hydroxyl radicals (•OH) and facilitating the degradation of AZO. Under optimal conditions, when pH = 3, the rate of AZO removal by the HA/ZVI/SPC system reached 99.0 % in 15 min, while the HA/ZVC/SPC system required 50 min to reach 99.1 % removal. Both of the tested HA/zero-valent metal/SPC processes produced •OH, carbonate radicals (CO3·-), superoxide radicals (O2·-) and singlet oxygen (1O2), among which, •OH appeared to be the main reactant responsible for AZO removal. Furthermore, it was found that •OH reacted with trace levels of carbonate ions to generate other reactive oxygen species and promote AZO degradation. The addition of HA not only slowed down the surface passivation of zero-valent metals, but also promoted the conversion of high-valent metal ions to low-valent metal ions, resulting in the generation of more reactive oxygen species within the system. In addition, the degradation intermediates were identified by LC-MS analysis and density-functional theory (DFT), allowing the possible AZO degradation pathways to be proposed.

Natural diterpene carrier-free hydrogel enhances antigen presentation and intensifies T cell activation for tumor immunotherapy

Although immunotherapy has revolutionized cancer treatment, the low immunogenicity, insufficient T cells intratumoral infiltration and defective antigen presentation in the “cold” tumor microenvironment limit its clinical application. To address this challenge, enlightened by the clinical combined application of antitumor herb medicines, we developed a carrier-free hydrogel KEEM by integrating multiple natural active lipophilic components with manganese ions into a natural co-assembled ternary system. The KEEM hydrogel induced the formation of hydroxyl radicals by Fenton-like reactions, leading to apoptosis, while simultaneously inducing tumor cell ferroptosis through the system xc−-GSH-GPX4 axis. Subsequent release of damage-associated molecular patterns (DAMPs) proved the emergence of immunogenic cell death (ICD). Additionally, manganese ions could directly activate the cGAS-STING pathway, further amplifying the immunostimulatory effects. This synergistic effect promoted dendritic cell maturation thus enhancing antigen presentation, and mediating the change of tumor microenvironment (TME) from “cold” to “hot”. In hepatoma ascites and melanoma models, KEEM combined with immune checkpoint blockade and adoptive T cell therapy respectively demonstrated promising anti-tumor effects in vivo, meanwhile showing excellent biocompatibility and biosafety. Thus, the combination of this multi-diterpenoids carrier-free hydrogel with immunotherapy offers a new strategy for clinical immune-refractory tumor treatment.

Injectable hydrogel assisted formation of hydroxyl radical generating bioreactor enables photothermally enhanced chemodynamic and immunotherapy

Photothermal therapy and chemodynamic therapy (CDT), two recently invented cancer treatments, have shown to be effective in potentiating immunotherapy through causing immunogenic cancer cell death. The rational integration of these two therapeutic modalities poses a formidable challenge in eliciting robust immunotherapy. Herein, an injectable hydrogel based bioreactor comprising of glucose oxidase (GOx), copper sulfide (CuS) nanoparticles, and poly (ethylene glycol) double acrylate (PEGDA) is prepared to potentiate immune checkpoint blockade (ICB) therapy. GOx can in situ convert glucose to hydrogen peroxide (H2O2) and gluconic acid, the latter of which further promotes the decomposition of H2O2 to hydroxyl radicals by creating an acidic microenvironment to benefit the pH-dependent Fenton-like catalytic reaction of Cu+, particularly in synergizing with near infrared (NIR) light exposure. Such catalytic couple of GOx and CuS together with NIR light exposure is efficient in inducing immunogenic cancer cell death. Additionally, GOx reprogrammed tumor immunosuppressive microenvironment by reducing lactate levels. Upon being fixed inside tumors with PEGDA hydrogel, such in situ formed bioreactor effectively suppresses the growth of 4T1 orthotopic murine breast cancers in Balb/c mice together with 808 nm laser exposure. Furthermore, such bioreactor enabled photothermally enhanced CDT could also synergize with anti-PD-L1 immunotherapy to more effectively suppress the growth of primary tumors and distant tumors. This study highlights that such NIR light and reactive oxygen species dual responsive bioreactor is robust to potentiate ICB immunotherapy.