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Gut microbial preparations are widely used in treating intestinal diseases but show mixed success. In this study, we found that the therapeutic efficacy of A. muciniphila for dextran sodium sulfate (DSS)-induced colitis as well as intestinal radiation toxicity was ~50%, and mice experiencing a positive prognosis harbored a high frequency of A. muciniphila in the gastrointestinal (GI) tract. Stable GI colonization of A. muciniphila elicited more profound shifts in the gut microbial community structure of hosts. Coexisting with A. muciniphila facilitated proliferation and reprogrammed the gene expression profile of Lactobacillus murinus, a classic probiotic that overtly responded to A. muciniphila addition in a time-dependent manner. Then, a magnetic-drove, mannose-loaded nanophase material was designed and linked to the surface of A. muciniphila. The modified A. muciniphila exhibited enhancements in inflammation targeting and intestinal colonization under an external magnetic field, elevating the positive-response rate and therapeutic efficacy against intestinal diseases. However, the unlinked cocktail containing A. muciniphila and the delivery system only induced negligible improvement of therapeutic efficacy. Importantly, heat-inactivated A. muciniphila lost therapeutic effects on DSS-induced colitis and was even retained in the GI tract for a long time. Further investigations revealed that the modified A. muciniphila was able to drive M2 macrophage polarization by upregulating the protein level of IL-4 at inflammatory loci. Together, our findings demonstrate that stable colonization of live A. muciniphila at lesion sites is essential for its anti-inflammatory function.

A new way of thinking on remodelling the design guidelines of anticancer drugs is demonstrated via learning from the metabolism of exogenous selenite in human body, and achieving multidimensional imaging-guided therapy with strong tumour-selectivity.

ICG-loaded and 125I-labeled theranostic nanosystem with high biocompatibility for FLI/SPECT-navigated PTT/PDT of breast cancer.

Sepsis is a life-threatening disease caused by systemic bacterial infections, with high morbidity and mortality worldwide. As the standard treatment for sepsis, antibiotic therapy faces the challenge of impaired macrophages and drug-resistant bacteria. In this study, we developed a membrane-camouflaged metal-organic framework (MOF) system for plasmid DNA (ip/iDNA) delivery to combat sepsis. The antimicrobial gene LL37 was efficiently encapsulated in the pH-sensitive MOF, and the nanoparticles were decorated with macrophage membranes in a compatible manner. Macrophage membrane coating allows targeted delivery of LL37 to macrophages and creates macrophage factories for the continuous generation of antimicrobial peptides. Compared to naked nanoparticles, primary bone marrow mesenchymal macrophage membrane-modified nanoparticles greatly improved the survival rate of immunodeficient septic mice through the synergistic effect of efficient gene therapy and inflammatory cytokine sequestration. This study demonstrates an effective membrane biomimetic strategy for efficiently deliveringip/iDNA, offering an excellent option for overcoming sepsis.

Figure S1. Cell viability of unstimulated A2780 cell line (A and B) or selected A2780 cell line. Figure S2. Cell viability of Kuramochi, OVSAHO, Saos-2, HepG2, and T98G cells treated with pTC-1 for 24, 48 and 72 h. Figure S3. Cell viability of A2780cis or HeLa cells without or with addition of methyladenine (2 or 5 mM) in the presence of pTC-1 for 24, 48 and 72h. Figure S4. CLSM images of PI (red) and FITC-annexin V (green) stained HeLa cells. Scheme S1. Molecular structure of NBD-pTC-1.

Loss of Lon1 in plant mitochondria led to stunted plant growth and accumulation of nuclear-encoded mitochondrial proteins, including Lon1 substrates, while mitochondrial-encoded proteins typically decreased in abundance. Lon1 mutants contained protein aggregates in the mitochondria matrix which were enriched in PPR-containing proteins and ribosomal subunits of the translation apparatus and were slowed in mitochondrial RNA splicing, editing and general translation rate. Transcriptome analysis showed multiple organellar unfolded protein responses involving ethylene biosynthesis were induced by either Lon1 loss, mitochondrial ribosomal protein loss, translation or respiratory inhibition and most were regulated by the mitochondrial retrograde signaling pathway dependent on the transcription factor NAC017. The short hypocotyl inlon1mutants during skotomorphogenesis was partially rescued by ethylene inhibitors and mutants showed higher ethylene production rates than wildtype. Together this provides multiple steps in the link between loss of Lon1 and its whole plant phenotype.Single Sentence SummaryLon1 knockout inhibits mitochondrial-encoded gene translation and induces retrograde signaling involving unfolded protein responses.

Breast cancer is the leading cause of cancer death among women and almost all of the breast cancer-caused mortality is related to metastasis. It has been reported that glucocorticoid facilitates the metastasis of breast cancer in mice, and mifepristone can antagonize the effect of glucocorticoid. Paclitaxel is one of the important drugs in the treatment of breast cancer. Mifepristone combined with paclitaxel may be an effective strategy for anti-metastasis of breast cancer. However, the inherent defects of them in short blood circulation half-life and lack of tumor targeting not only limit their effectiveness but also cause adverse reactions. Therefore, our aim is to explore a novel protocol against breast cancer metastasis, further optimize its therapeutic efficacy by nano-delivery system, and initially explore its mechanism. Herein, a paclitaxel-conjugated and mifepristone-loaded hydrogel (PM-nano) was prepared by self-assembly. Its characterizations were studied. The anti-metastasis effect was also evaluated in vitro and in vivo. Its mechanism was also explored by western blot assay. The resulted PM-nano was developed with favorable water solubility and good biocompatibility. Moreover, PM-nano displayed increased cell uptake property and stimulated drug release in tumor micro-acidic environment. PM-nano was more effective in inhibiting the proliferation and metastasis of breast cancer than other groups in vitro and in vivo. PM-nano might inhibit metastasis through glucocorticoid receptor/receptor tyrosine kinase-like orphan receptor 1 and matrix metalloproteinases. Taken together, PM-nano exhibited superior anti-metastasis effect against breast cancer and excellent biocompatibility in vitro and in vivo, providing a new option for anti-metastasis.

Radiotherapy is one of the conventional tumor treatments, while its abscopal therapeutic efficacy is severely hampered by the immunosuppressive tumor microenvironment. To address this challenge, we herein report on the morphology-adaptable peptide-based therapeutics for efficiently reversing the immunosuppression in the combinatorial radio-immunotherapy through simultaneous checkpoint blocking and induction of immunogenic cell death. The peptide-based therapeutics were created via co-assembling a pentapeptide containing a 4-amino proline residue with its derivatives containing IDO-1 inhibitor NLG919. The resulting therapeutics underwent pH-adaptable morphological transformation between nanofibrils and nanoparticles and released NLG919 upon GSH cleavage. In vivo studies confirmed that the pH-adaptable morphologies of the therapeutics facilitated their tumor accumulation and retention at tumor sites compared to morphology-persistent counterparts, thus resulting in efficient delivery of IDO-1 inhibitors. Simultaneously treating the tumor-bearing mice with the therapeutics and external γ-ray radiation boosted the tumor immunogenicity via inducing ICD cascade of the tumor cells and reverse the immunosuppressive tumor microenvironment due to the inhibition of IDO-1 for depletion of tryptophan. Our findings strongly demonstrate that the morphology-adaptable peptide-based therapeutics exhibit the capability to reverse the immunosuppressive tumor microenvironment during irradiation, thus providing a new strategy for the combinatorial radio-immunotherapy.

NIR-activated therapies based on light-responsive drug delivery systems are emerging as a remote-controlled method for cancer precise therapy. In this work, fluorescent dye indocyanine green (ICG)-conjugated and bioactive compound gambogic acid (GA)-loaded polymeric micelles (GA@PEG-TK-ICG PMs) were smoothly fabricated via the self-assembly of the reactive oxygen species (ROS)-responsive thioketal (TK)-linked amphiphilic polymer poly(ethyleneglycol)-thioketal-(indocyanine green) (PEG-TK-ICG). The resultant micelles demonstrated increased resistance to photobleaching, enhanced photothermal conversion efficiency, NIR-controlled drug release behavior, preferable biocompatibility, and excellent tumor accumulation performance. Moreover, upon an 808 nm laser irradiation, the micellar photoactive chromophore ICG converted the absorbed optical energy to both hyperthermia for photothermal therapy (PTT) and ROS as the feedback trigger to the micelles for the tumor-specific release of GA, which could serve as not only a chemotherapeutic drug to directly kill tumor cells but also a heat shock protein 90 (HSP90) inhibitor to realize the photothermal sensitization. As a result, an extremely high tumor inhibition rate (97.9%) of mouse 4 T1 breast cancer models was achieved with negligible side effects after the chemo-photothermal synergistic therapy. This NIR-activated nanosystem with photothermal self-sensitization function may provide a feasible option for the effective treatment of aggressive breast cancers.

Multimodality imaging-navigated precise phototherapy has been well-established as a promising strategy for enhancing the diagnostic and therapeutic efficiency of cancer in preclinical trials. However, proper theranostic agents with adequate biosafety and biological efficacy as well as simple components and preparations are still in great demand to promote the clinical translation of this regimen. Here, we developed a multifunctional nanosystem based on the self-assembly of FDA-approved indocyanine green (ICG) and

Hydrogen-atom transfer mediated by earth-abundant transition-metal hydrides (M-Hs) has emerged as a powerful tool in organic synthesis. Current methods to generate M-Hs most frequently rely on oxidatively initiated hydride transfer. Herein, we report a reductive approach to generate Co-H, which allows for canonical hydrogen evolution reactions to be intercepted by hydrogen-atom transfer to an alkene. Electroanalytical and spectroscopic studies provided mechanistic insights into the formation and reactivity of Co-H, which enabled the development of two new alkene hydrofunctionalization reactions.

The use of conventional antibiotics has rapidly declined due to the development of antibiotic resistance. Therefore, there is an urgent need for the development of novel vehicles to facilitate effective antibiotics delivery, especially for bacteria that form biofilm. Herein, we designed a library of pH-sensitive polymer vehicles with pKa values ranging from 6.2-5.0. We found that pKa values located into 5.3-5.7 displayed certain antibacterial effect and effective biofilm elimination. The antibacterial effect the copolymer vehicles is highly pKa dependent. Regardless of physical environment or pH 5.6 conditions, biofilm elimination improved silightly. Among the five vehicles, the copolymer (PEPB36/35) with pKa about 5.7 not only exhibited the best biosafety, but also significantly improved the biocompatibility of antibiotics triclosan (TCS). Moreover, PEPB36/35 nanoparticles (NPs) destroyed cell membranes and promoted cargos into cells under an acidic environment. The formed of PEPB36/35@TCS NPs spray was able to kill Methicillin Resistant Staphylococcus Aureus (MRSA) in biofilm and accelerate infected wound healing, which reduced inflammation and promoted angiogenesis. Collectively, these findings affirm that the designed pH-sensitive vehicles improve antibacterial efficacy of TCS in killing bacteria in biofilm.

In cancer radiotherapy, the lack of fixed DNA damage by oxygen in hypoxic microenvironment of solid tumors often leads to severe radioresistance. Nitric oxide (NO) is a potent radiosensitizer that acts in two ways. It can directly react with the radical DNA thus fixing the damage. It also normalizes the abnormal tumor vessels, thereby increasing blood perfusion and oxygen supply. To achieve these functions, the dosage and duration of NO treatment need to be carefully controlled, otherwise it will lead to the exact opposite outcomes. However, a delivery method that fulfills both requirements is still lacking. A NO depot is designed for the control of NO releasing both over quantity and duration for hypoxic tumor vessel normalization and radiosensitization. In B16-tumor-bearing mice, the depot can provide low dosage NO continuously and release large amount of NO immediately before irradiation for a short period of time. These two modes of treatment work in synergy to reverse the radioresistance of B16 tumors more efficiently than releasing at single dosage.

A new strategy for a viologen complex, (HV)[Co(H2O)6](p-BDC)2(DMF)·H2O (1) (p-BDC = 1,4-benzene dicarboxylate, DMF = N,N-dimethylformamide), was designed by keeping highly symmetrical hydrogen bonding and maximum π⋅⋅⋅π stacking interactions. By the reaction of Co(NO3)2·6H2O with 1,1′-bis(n-hexyl)-4,4′-bipyridinium dibromide (HVBr2) and 1,4-benzenedicarboxylic acid (p-H2BDC), the viologen complex 1 was prepared with monoclinic space group P 2/n, which is constituted by HV2+ cation, [Co(H2O)6]2+ cation, DMF and constitution water as well as two p-BDC2− anions to form a supramolecular 3D framework. The viologen complex 1 exhibits photochromic and thermochromic property. The types and regions of intercontacts in viologen complex 1 were illustrated by Hirshfeld surface and two-dimensional (2D) fingerprint plots in crystal stacking. The frontier molecular orbital was evaluated to explain the matching rules between electron acceptor and donor at the density functional theory (DFT)-B3LYP/6-311 (d, p) level. It is of great signifcance to investigate inter/intramolecular interaction and chromic property of viologen complex 1 and provide theoretical guidance for the self assembly design and decoration of viologen complexes.

The elimination of reactive oxygen species (ROS) caused by glutathione (GSH) is a fundamental concern in the oxidative stress therapy (OST) of tumors. This is the first report of copper phosphate nanospheres coated by poly (ethylene glycol) diacrylate (Cu3(PO4)2@PEGDA) which act as nanozymes to amplify the anti-tumor effects of OST. Cu3(PO4)2@PEGDA not only catalyzes the generation of ˙OH from H2O2 but also consumes GSH, which is counterproductive to the role of ˙OH. Moreover, the photothermal properties of Cu3(PO4)2@PEGDA further enhances the outcome of the OST when exposed to an 808 nm laser. Another novelty lies in that a new PEGylation strategy of peroxidase-like nanozymes is proposed, in which the Cu3(PO4)2 cores work as internal heaters and radical generators, which are necessary to initiate the radical polymerization of PEGDA. An elaborate core-shell nanostructure is obtained since the polymerization prefers to take place in the vicinity of the cores, overcoming the drawbacks of traditional PEGylation methods which include invalid polymerization far away from the cores and easy core-shell disassembly during applications.

Three Mn–viologen complexes containing 1-carboxyethyl-4,4′-bipyridinium (CEbpy) were synthesized, [Mn(H2O)6]·2(CEbpy)·(TPDC)·3H2O (1), [Mn(H2O)6]·2(CEbpy)·(m-BDC)·2H2O (2) and [Mn(H2O)6]·2(CEbpy)·(p-BDC)·2H2O (3) (H2TPDC = thiophene-2,5-dicarboxylic acid, m-H2BDC = 1,3-benzenedicarboxylic acid, p-H2BDC = 1,4-benzenedicarboxylic acid), which were investigated based on crystal structures, photochromism, molecular orbitals, Hirshfeld surfaces and 2D fingerprint plots. All three complexes present sensitive photoresponse behaviors in the sequence of 1 ≫ 3 > 2, due to the existence of electron-deficient viologen fractions. Compound 1 exhibits two electron transfer modes: intramolecular and intermolecular electron transfer. Compounds 2 and 3 exhibit intramolecular electron transfer. The density functional theory (DFT)-B3LYP/6-311(d,p) method was used to gain insight into the donor–acceptor structures, matching rules between CEbpy and the acid moiety as well as inter/intramolecular atom–atom close contacts based on the fraction of intercontact.

Electrochemistry has recently gained increased attention as a versatile strategy for achieving challenging transformations at the forefront of synthetic organic chemistry. Electrochemistry’s unique ability to generate highly reactive radical and radical ion intermediates in a controlled fashion under mild conditions has inspired the development of a number of new electrochemical methodologies for the preparation of valuable chemical motifs. Particularly, recent developments in electrosynthesis have featured an increased use of redox-active electrocatalysts to further enhance control over the selective formation and downstream reactivity of these reactive intermediates. Furthermore, electrocatalytic mediators enable synthetic transformations to proceed in a manner that is mechanistically distinct from purely chemical methods, allowing for the subversion of kinetic and thermodynamic obstacles encountered in conventional organic synthesis. This review highlights key innovations within the past decade in the area of synthetic electrocatalysis, with emphasis on the mechanisms and catalyst design principles underpinning these advancements. A host of oxidative and reductive electrocatalytic methodologies are discussed and are grouped according to the classification of the synthetic transformation and the nature of the electrocatalyst.

Although the shortcomings of small molecular antitumor drugs were efficiently improved by being entrapped into nanosized vehicles, premature drug release and insufficient tumor targeting demand innovative approaches that boost the stability and tumor responsiveness of drug-loaded nanocarriers. Here, we show the use of the core cross-linking method to generate a micelle with enhanced drug encapsulation ability and sensitivity of drug release in tumor. This kind of micelle could increase curcumin (Cur) delivery to HeLa cells in vitro and improve tumor accumulation in vivo. We designed and synthesized the core cross-linked micelle (CCM) with polyethylene glycol and folic acid-polyethylene glycol as the hydrophilic units, pyridyldisulfide as the cross-linkable and hydrophobic unit, and disulfide bond as the cross-linker. CCM showed spherical shape with a diameter of 91.2 nm by the characterization of dynamic light scattering and transmission electron microscope. Attributed to the core cross-linking, drug-loaded CCM displayed higher Nile Red or Cur-encapsulated stability and better sensitivity to glutathione than noncross-linked micelle (NCM). Cellular uptake and in vitro antitumor studies proved the enhanced endocytosis and better cytotoxicity of CCM-Cur against HeLa cells, which had a high level of glutathione. Meanwhile, the folate receptor-mediated drug delivery (FA-CCM-Cur) further enhanced the endocytosis and cytotoxicity. Ex vivo imaging studies showed that CCM-Cur and FA-CCM-Cur possessed higher tumor accumulation until 24 hours after injection. Concretely, FA-CCM-Cur exhibited the highest tumor accumulation with 1.7-fold of noncross-linked micelle Cur and 2.8-fold of free Cur. By combining cross-linking of the core with active tumor targeting of FA, we demonstrated a new and effective way to design nanocarriers for enhanced drug encapsulation, smart tumor responsiveness, and elevated tumor accumulation.

We have developed a co-assembled nanosystem based on fenofibrate and ketoprofen by tactfully utilizing their simultaneous benzophenone interaction, which greatly enhances the bioavailability of fenofibrate and plays a role in the dual-targeted treatment of NAFLD by reducing hepatic lipid accumulation and inflammatory responses.

We constructed a novel supramolecular hydrogel by carrying out a coassembly of cisplatin and short naproxen-capped peptides. This procedure boosted the radiosensitization effect of cisplatin by increasing the number of Pt-DNA adducts, arresting the cell cycle, and inhibiting cyclooxygenase-2.

To study the effect of metal ions on the photochromic behaviors of CPs, three new isostructural coordination polymers (CPs) based on a neutral viologen moiety, 1,1'-bis(3-carboxylatobenzyl)-4,4'-bipyridinium (bcbpy), have been obtained by choosing 1,2,4,5-benzenetetracarboxylic acid (H4BTEC) to coordinate with different metal ions, {[M(H2O)6][M(BTEC)(H2O)4]·(bcbpy)·4H2O}n (M = Co (1), Ni (2), Zn (3)), all of which exhibit metal-dependent photochromism and adjustable photosensitivity. Compounds 1 and 2 are only sensitive to UV light, while compound 3 is sensitive to sunlight, UV light and X-ray (Mo). The comparison of the photochromic behaviors of the three CPs indicates that the metal ions play an important role in regulating their photochromic properties.

Based on a bipyridinium carboxylate ligand 1,1′-bis(3-carboxylatobenzyl)-(4,4′-bipyridinium)-dichloride (H2bcbpyCl2), three new coordination polymers {[Co0.5(bcbpy)0.5(H2O)2](p-BDC)0.5·H2O}n (1) {[Ni(bcbpy)(H2O)4](p-BDC)·2H2O}n (2) and [Zn2(bcbpy)(BTEC)(H2O)2·6H2O]n (3) are designed and synthesized by varying the benzenecarboxylic acids (1,4-benzenedicarboxylic acid = p-H2BDC, 1,2,4,5-benzenetetracarboxylic acid = H4BTEC) to adjust the coordination mode between the viologen ligand and metal ions. Single crystal structure analyses reveal that compounds 1 and 2 both exhibit one-dimensional (1D) chain-like structure, while compound 3 exhibits two-dimensional (2D) layered architecture. Furthermore, due to the formation of viologen radicals, reversible color changes for three compounds can be observed in the air upon sunlight, UV-light and X-ray irradiation. Particularly, compound 3 has high photosensitivity, giving an eye-detectable color change after exposure to sunlight in air within 1 min. In addition, the photoproducts for the three compounds exhibit an ultralonglived charge-separated state.

In contrast to the rapid growth of synthetic electrochemistry in recent years, enantioselective catalytic methods powered by electricity remain rare. In this work, we report the development of a highly enantioselective method for the electrochemical cyanophosphinoylation of vinylarenes. A new family of serine-derived chiral bisoxazolines with ancillary coordination sites were identified as optimal ligands.

Green housing (GH) has been regarded as an effective and sustainable solution for alleviating the energy crisis and reducing environmental pressure in China, but currently, consumers rarely select GH when purchasing houses. This study aims to explore the influencing factors of consumers’ willingness to purchase GH in China. The research model was developed using the theory of planned behaviour (TPB) and norm activation theory (NAM), and it tested hypotheses using data from a questionnaire collected from 355 consumers in Shandong Province, China. Partial least squares structural equation model analysis showed that the testing of hypotheses was significant, in which personal norm and perceived behavioural control as direct influencing variables had a significant influence on consumers’ willingness to purchase GH. Therefore, GH purchase is driven by the comprehensive rational and moral factors of consumers. In addition, part of the mediating effect testing reveals that subjective norm indirectly influences personal norm through perceived behavioural control, and awareness of consequences indirectly influences personal norm through ascription of responsibility. In general, the integration of the structure of TPB and NAM, comprehensive self-interest (rational) and altruism (moral) aspects significantly improve the prediction capability of the theoretical framework. Results show the influence of the consumer to GH purchase willingness with regard to internal psychological factors, design and implementation of related policies and measures for the government to provide a frame of reference.

Acquired drug resistance remains a challenge in chemotherapy. Here we show enzymatic, in situ assembling of cholesterol derivatives to act as polypharmaceuticals for selectively inducing death of cancer cells via multiple pathways and without inducing acquired drug resistance. A conjugate of tyrosine and cholesterol (TC), formed by enzyme-catalyzed dephosphorylation of phosphorylate TC, self-assembles selectively on or in cancer cells. Acting as polypharmaceuticals, the assemblies of TC augment lipid rafts, aggregate extrinsic cell death receptors (e.g., DR5, CD95, or TRAILR), modulate the expression of oncoproteins (e.g., Src and Akt), disrupt the dynamics of cytoskeletons (e.g., actin filaments or microtubules), induce endoplasmic reticulum stress, and increase the production of reactive oxygen species, thus resulting in cell death and preventing acquired drug resistance. Moreover, the assemblies inhibit the growth of platinum-resistant ovarian cancer tumor in a murine model. This work illustrates the use of instructed assembly (iA) in cellular environment to form polypharmaceuticals in situ that not only interact with multiple proteins, but also modulate membrane dynamics for developing novel anticancer therapeutics. Implications: As a multifaceted strategy for controlling cancer cell death, iA minimized acquired resistance of cancer cells, which is a new strategy to amplify the genetic difference between cancer and normal cells and provides a promise for overcoming drug resistance in cancer therapy. Visual Overview: http://mcr.aacrjournals.org/content/molcanres/17/4/907/F1.large.jpg.

The self-assembly reaction of TM2+ (TM = Zn, Cd), 1,3-benzenedicarboxylic acid (m-H2BDC), and ethyl viologen cation (EV2+ = 1,1′-bis(ethyl)-4,4′-bipyridinium dication) leads to two new host-guest MOFs {(EV)0.5[TM1.5(m-BDC)2]}n (1, Zn; 2, Cd), of which TM1.5(m-BDC)2]2- acts as host anion and EV2+ acts as guest cation. The two compounds have different chromic properties. Compound 1 exhibits both electron-transfer (ET) photochromism under indoor light, sunlight and UV light irradiation and ET thermochromism, while compound 2 only exhibits ET photochromism under sunlight and UV light irradiation. Compounds 1 and 2 have the same structure except for different coordination metal ions, the effects of metal ions on the chromic behaviors of two compounds have been explored.

Photodynamic therapy (PDT) has attracted much attention in cancer treatment due to its tumor selectivity and noninvasive nature. Recent studies have demonstrated that PDT mediated reactive oxygen species (ROS) generation in tumor microenvironment (TME) synergistically improves the efficacy of immune checkpoint blockade (ICB) therapy. However, the instability and short half-life of the ROS generated by PDT limit its clinical applications. Herein, a coassembled peptide hydrogel comprising two short peptides that contained the same assembly unit, Ce6-KKFKFEFEF (KEF-Ce6) and RRRRRRRR-KFKFEFEF (KEF-R8) is developed. When exposed to 635 nm laser irradiation, KEF-Ce6 released ROS, while KEF-R8 plays as nitric oxide (NO) donor. Subsequently, ROS reacts with NO to produce reactive nitrogen species (RNS). Both in vitro and in vivo experiments prove that converting ROS into more cytotoxic RNS caused intense cell death. Importantly, it is observed that tumor-associated macrophages (TAMs) are polarized to proinflammatory types (M1-type) by the RNS-based PDT. The increase of M1 macrophages relieves the immunosuppressive situation in TME. Thus, when combined with αPD-L1 treatment, the survival time of tumor-bearing mice is prolonged. Overall, a simple yet efficient coassembled hydrogel that can cascade release ROS/NO/RNS and strengthen antitumor T cell responses to boost cancer immunotherapy by reprogramming TAMs is provided.

Clinical wound management of radiation-induced skin injury (RSI) remains a great challenge due to acute injuries induced by excessive reactive oxygen species (ROS), and the concomitant repetitive inflammatory microenvironment caused by an imbalance in macrophage homeostasis. Herein, a cutaneous extracellular matrix (ECM)-inspired glycopeptide hydrogel (GK@TA

The elimination of reactive oxygen species (ROS) caused by glutathione (GSH) is a fundamental concern in the oxidative stress therapy (OST) of tumors. This is the first report of copper phosphate nanospheres coated by poly (ethylene glycol) diacrylate (Cu