Precision treatment of viral pneumonia through macrophage-targeted lipid nanoparticle delivery.

Macrophages are integral components of the innate immune system, playing a dual role in host defense during infection and pathophysiological states. Macrophages contribute to immune responses and aid in combatting various infections, yet their production of abundant proinflammatory cytokines can lead to uncontrolled inflammation and worsened tissue damage. Therefore, reducing macrophage-derived proinflammatory cytokine release represents a promising approach for treating various acute and chronic inflammatory disorders. However, limited macrophage-specific delivery vehicles have hindered the development of macrophage-targeted therapies. In this study, we screened a pool of 112 lipid nanoparticles (LNPs) to identify an optimal LNP formulation for efficient siRNA delivery. Subsequently, by conjugating the macrophage-specific antibody F4/80 to the LNP surface, we constructed MacLNP, an enhanced LNP formulation designed for targeted macrophage delivery. In both in vitro and in vivo experiments, MacLNP demonstrated a significant enhancement in targeting macrophages. Specifically, delivery of siRNA targeting TAK1, a critical kinase upstream of multiple inflammatory pathways, effectively suppressed the phosphorylation/activation of NF-kB. LNP-mediated inhibition of NF-kB, a key upstream regulator in the classic inflammatory signaling pathway, in the murine macrophage cell line RAW264.7 significantly reduced the release of proinflammatory cytokines after stimulation with the viral RNA mimic Poly(I:C). Finally, intranasal administration of MacLNP-encapsulated TAK1 siRNA markedly ameliorated lung injury induced by influenza infection. In conclusion, our findings validate the potential of targeted macrophage interventions in attenuating inflammatory responses, reinforcing the potential of LNP-mediated macrophage targeting to treat pulmonary inflammatory disorders.

Platelet-Mimicking Nanosponges for Functional Reversal of Antiplatelet Agents.

BACKGROUND: During long-term antiplatelet agents (APAs) administration, patients with thrombotic diseases take a fairly high risk of life-threatening bleeding, especially when in need of urgent surgery. Rapid functional reversal of APAs remains an issue yet to be efficiently resolved by far due to the lack of any specific reversal agent in the clinic, which greatly restricts the use of APAs. METHODS: Flow cytometry analysis was first applied to assess the dose-dependent reversal activity of platelet-mimicking perfluorocarbon-based nanosponges (PLT-PFCs) toward ticagrelor. The tail bleeding time of mice treated with APAs followed by PLT-PFCs was recorded at different time points, along with corresponding pharmacokinetic analysis of ticagrelor and tirofiban. A hemorrhagic transformation model was established in experimental stroke mice with thrombolytic/antiplatelet therapy. Magnetic resonance imaging was subsequently applied to observe hemorrhage and thrombosis in vivo. Further evaluation of the spontaneous clot formation activity of PLT-PFCs was achieved by clot retraction assay in vitro. RESULTS: PLT-PFCs potently reversed the antiplatelet effect of APAs by competitively binding with APAs. PLT-PFCs showed high binding affinity comparable to fresh platelets in vitro with first-line APAs, ticagrelor and tirofiban, and efficiently reversed their function in both tail bleeding and postischemic-reperfusion models. Moreover, the deficiency of platelet intrinsic thrombotic activity diminished the risk of thrombogenesis. CONCLUSIONS: This study demonstrated the safety and effectiveness of platelet-mimicking nanosponges in ameliorating the bleeding risk of different APAs, which offers a promising strategy for the management of bleeding complications induced by antiplatelet therapy.

Dual-Locked Fluorescent Probes Activated by Aminopeptidase N and the Tumor Redox Environment for High-Precision Imaging of Tumor Boundaries.

Clear delineation of tumor margins is essential for accurate resection and decreased recurrence rate in the clinic. Fluorescence imaging is emerging as a promising alternative to traditional visual inspection by surgeons for intraoperative imaging. However, traditional probes lack accuracy in tumor diagnosis, making it difficult to depict tumor boundaries accurately. Herein, we proposed an offensive and defensive integration (ODI) strategy based on the "attack systems (invasive peptidase) and defense systems (reductive microenvironment)" of multi-dimensional tumor characteristics to design activatable fluorescent probes for imaging tumor boundaries precisely. Screened out from a series of ODI strategy-based probes, ANQ performed better than traditional probes based on tumor unilateral correlation by distinguishing between tumor cells and normal cells and minimizing false-positive signals from living metabolic organs. To further improve the signal-to-background ratio in vivo, derivatized FANQ, was prepared and successfully applied to distinguish orthotopic hepatocellular carcinoma tissues from adjacent tissues in mice models and clinical samples. This work highlights an innovative strategy to develop activatable probes for rapid diagnosis of tumors and high-precision imaging of tumor boundaries, providing more efficient tools for future clinical applications in intraoperative assisted resection.

RIG-I Promotes Tumorigenesis and Confers Radioresistance of Esophageal Squamous Cell Carcinoma by Regulating DUSP6.

We investigated the expression and biological function of retinoic acid inducible gene I (RIG-I) in esophageal squamous cell carcinoma (ESCC). Materials and methods: An immunohistochemical analysis was performed on 86 pairs of tumor tissue and adjacent normal tissue samples of patients with ESCC. We generated RIG-I-overexpressing ESCC cell lines KYSE70 and KYSE450, and RIG-I- knockdown cell lines KYSE150 and KYSE510. Cell viability, migration and invasion, radioresistance, DNA damage, and cell cycle were evaluated using CCK-8, wound-healing and transwell assay, colony formation, immunofluorescence, and flow cytometry and Western blotting, respectively. RNA sequencing was performed to determine the differential gene expression between controls and RIG-I knockdown. Tumor growth and radioresistance were assessed in nude mice using xenograft models. RIG-I expression was higher in ESCC tissues compared with that in matched non-tumor tissues. RIG-I overexpressing cells had a higher proliferation rate than RIG-I knockdown cells. Moreover, the knockdown of RIG-I slowed migration and invasion rates, whereas the overexpression of RIG-I accelerated migration and invasion rates. RIG-I overexpression induced radioresistance and G2/M phase arrest and reduced DNA damage after exposure to ionizing radiations compared with controls; however, it silenced the RIG-I enhanced radiosensitivity and DNA damage, and reduced the G2/M phase arrest. RNA sequencing revealed that the downstream genes DUSP6 and RIG-I had the same biological function; silencing DUSP6 can reduce the radioresistance caused by the overexpression of RIG-I. RIG-I knockdown depleted tumor growth in vivo, and radiation exposure effectively delayed the growth of xenograft tumors compared with the control group. RIG-I enhances the progression and radioresistance of ESCC; therefore, it may be a new potential target for ESCC-targeted therapy.

LncRNA H19 Regulates Breast Cancer DNA Damage Response and Sensitivity to PARP Inhibitors via Binding to ILF2.

Although DNA damage repair plays a critical role in cancer chemotherapy, the function of lncRNAs in this process remains largely unclear. In this study, in silico screening identified H19 as an lncRNA that potentially plays a role in DNA damage response and sensitivity to PARP inhibitors. Increased expression of H19 is correlated with disease progression and with a poor prognosis in breast cancer. In breast cancer cells, forced expression of H19 promotes DNA damage repair and resistance to PARP inhibition, whereas H19 depletion diminishes DNA damage repair and increases sensitivity to PARP inhibitors. H19 exerted its functional roles via direct interaction with ILF2 in the cell nucleus. H19 and ILF2 increased BRCA1 stability via the ubiquitin-proteasome proteolytic pathway via the H19- and ILF2-regulated BRCA1 ubiquitin ligases HUWE1 and UBE2T. In summary, this study has identified a novel mechanism to promote BRCA1-deficiency in breast cancer cells. Therefore, targeting the H19/ILF2/BRCA1 axis might modulate therapeutic approaches in breast cancer.

Platelet-Membrane-Coated Nanoparticles Enable Vascular Disrupting Agent Combining Anti-Angiogenic Drug for Improved Tumor Vessel Impairment.

Compared with traditional chemotherapeutics, vascular disruption agents (VDAs) have the advantages of rapidly blocking the supply of nutrients and starving tumors to death. Although the VDAs are effective under certain scenarios, this treatment triggers angiogenesis in the later stage of therapy that frequently leads to tumor recurrence and treatment failure. Additionally, the nonspecific tumor targeting and considerable side effects also impede the clinical applications of VDAs. Here we develop a customized strategy that combines a VDA with an anti-angiogenic drug (AAD) using mesoporous silica nanoparticles (MSNs) coated with platelet membrane for the self-assembled tumor targeting accumulation. The tailor-made nanoparticles accumulate in tumor tissues through the targeted adhesion of platelet membrane surface to damaged vessel sites, resulting in significant vascular disruption and efficient anti-angiogenesis in animal models. This study demonstrates the promising potential of combining VDA and AAD in a single nanoplatform for tumor eradication.

In Vivo Imaging of Endogenously Produced HClO in Zebrafish and Mice Using a Bright, Photostable Ratiometric Fluorescent Probe.

A high brightness red fluorescent probe (S-BODIPY) has been developed for the sensitive and specific imaging of HClO/ClO- in vitro and in vivo. This probe exhibits some distinctive features such as excellent resistance to photobleaching, a high fluorescence brightness, high selectivity, as well as a good biocompatibility. Upon oxidation of the thio-ether group into sulfoxide, the probe showed a noticeable ratiometric fluorescence response toward ClO- with fast response (within 30 s) and a low detection limit (59 nM). The probe demonstrated the successful imaging of exogenous and endogenous HClO/ClO- in living HeLa cells, zebrafish, and mice with high signal-to-noise ratios. S-BODIPY allows for the real-time monitoring the level of ClO- in living cells by ratiometric fluorescence imaging, opening up exciting prospects to develop red and even near-infrared BODIPYs with high brightness and good photostability for in vivo imaging.

Targeting Delivery of Platelets Inhibitor to Prevent Tumor Metastasis.

Activated platelets have a high affinity for tumor cells, and consequently, they can protect tumor cells from environmental stress and immune attacks. Therefore, preventing platelet-tumor cell interaction can lead to the elimination of circulating tumor cells via natural killer cells and finally metastasis inhibition. It is also shown that CREKA (Cys-Arg-Glu-Lys-Ala), a tumor-homing pentapeptide, targets fibrin-fibronectin complexes that are found on the tumor stroma and the vessel walls. In this study, we linked CREKA to Ticagrelor, a reversible antagonist of the P2Y12 receptor on platelets. In vitro experiments indicated that CREKA-Ticagrelor could not only inhibit the platelet-induced migration of tumor cells with an invasive phenotype but also prevent tumor-platelet interaction. In vivo antitumor and antimetastasis results of this drug showed that CREKA-Ticagrelor could specifically target the tumor tissues within 24 h post intravenous injection and suppress lung metastasis. Meanwhile, by having this antiplatelet drug targeted, its side effects were minimized, and bleeding risk was decreased. Thus, CREKA-Ticagrelor offers an efficient antimetastatic agent.

Laparoscopic Surgery in the treatment of children with Choledochal Cyst.

OBJECTIVE: To evaluate the clinical effectiveness of laparoscopic surgery in the treatment of children with choledochal cyst. METHODS: Seventy-six children with congenital choledochal cyst who were admitted to our hospital between February 2016 and April 2017 were selected as research subjects. They were evenly divided into an observation group and a control group using random number table, 38 each group. Patients in the observation group underwent laparoscopic surgery, while patients in the control group underwent the traditional laparotomy. Surgery related indicators and prognosis were compared between the two groups. RESULTS: The incision size and intraoperative bleeding volume of the observation group were significantly smaller than those of the control group (P<0.05). The time of passage of flatus and time to take food of the observation group were easier than those of the control group, and the duration of hospitalization and parenteral nutrition of the former was significantly shorter than those of the latter, and the difference had statistical significance (P<0.05). The incidence of postoperative complications in the observation group was 2.6%, significantly lower than that in the control group (10.5%) (P<0.05). There was no recurrence in the observation group during the follow-up period, but there were 5 cases of recurrence (13.1%) in the control group; the difference was statistically significant (P<0.05). CONCLUSION: Compared with the traditional laparotomy, laparoscopic surgery conforms more to the concept of modern medical minimally invasive treatment and has a significant clinical effect in the treatment of congenital choledochal cyst in children. It can effectively promote the disappearance of clinical symptoms and signs, reduce the incidence of postoperative complications and disease recurrence, and improve the surgical efficacy, suggesting high clinical significance and application values.

Synthesis and spectroscopic properties of some novel BODIPY dyes.

BODIPY dyes have some unique properties including high fluorescence quantum yield, large extinction coefficiency, narrow absorption and emission band. However, most of BODIPY dyes display short emission wavelength and small Stokes shift, which limits their applications in biosensing and bioimaging in vivo. For bioimaging application, a fluorescent dye with long emission wavelength and large Stokes shift is highly desired. To push the absorption and emission spectrum of BODIPY to red and even far-red region, a COOEt group was introduced to the meso position, and some aromatic group was attached to the 3, 5 position of BODIPY core. The structure of resulting compounds were comfirmed by 1H NMR, 13C NMR and HR-MS. Dye-1 displays a strong UV-Vis absorption band centered at 536 nm and a sharp emission band is located at 592 nm, which is significantly red-shifted (80 nm) compared to ordinary BODIPY analogs. In addition, the meso-COOEt substituted BODIPYs exhibit high quantum yield and red to far-red emission. Notably surprisingly, the meso-COOEt substituted BODIPYs display almost separated UV-Vis absorption and emission spectra with a large Stokes shift (-60 nm). Time-dependent density functional theory calculations were conducted to understand the structure-optical properties relationship, and it was revealed that the large Stokes shift was resulted from the geometric change from the ground state to the first excited singlet state. The spectroscopic properties of these BODIPY dyes display very subtle solvent-dependence effect. Furthermore, BODIPY was tested for its ability of imaging in living cells. The results indicate that Dye-1 is a water-soluble and membrane-permeable probe. Therefore, these BODIPYs are a new family dyes with excellent spectroscopic properties and can be good candidates for bioimaging in living cells.

Anti-lymphangiogenesis for boosting drug accumulation in tumors.

The inadequate tumor accumulation of anti-cancer agents is a major shortcoming of current therapeutic drugs and remains an even more significant concern in the clinical prospects for nanomedicines. Various strategies aiming at regulating the intratumoral permeability of therapeutic drugs have been explored in preclinical studies, with a primary focus on vascular regulation and stromal reduction. However, these methods may trigger or facilitate tumor metastasis as a tradeoff. Therefore, there is an urgent need for innovative strategies that boost intratumoral drug accumulation without compromising treatment outcomes. As another important factor affecting drug tumor accumulation besides vasculature and stroma, the impact of tumor-associated lymphatic vessels (LVs) has not been widely considered. In the current research, we verified that anlotinib, a tyrosine kinase inhibitor with anti-lymphangiogenesis activity, and SAR131675, a selective VEGFR-3 inhibitor, effectively decreased the density of tumor lymphatic vessels in mouse cancer models, further enhancing drug accumulation in tumor tissue. By combining anlotinib with therapeutic drugs, including doxorubicin (Dox), liposomal doxorubicin (Lip-Dox), and anti-PD-L1 antibody, we observed improved anti-tumor efficacy in comparison with monotherapy regimens. Meanwhile, this strategy significantly reduced tumor metastasis and elicited stronger anti-tumor immune responses. Our work describes a new, clinically transferrable approach to augmenting intratumoral drug accumulation, which shows great potential to address the current, unsatisfactory efficacies of therapeutic drugs without introducing metastatic risk.

Influence of ionizable lipid tail length on lipid nanoparticle delivery of mRNA of varying length.

RNA-based therapeutics have gained traction for the prevention and treatment of a variety of diseases. However, their fragility and immunogenicity necessitate a drug carrier. Lipid nanoparticles (LNPs) have emerged as the predominant delivery vehicle for RNA therapeutics. An important component of LNPs is the ionizable lipid (IL), which is protonated in the acidic environment of the endosome, prompting cargo release into the cytosol. Currently, there is growing evidence that the structure of IL lipid tails significantly impacts the efficacy of LNP-mediated mRNA translation. Here, we optimized IL tail length for LNP-mediated delivery of three different mRNA cargos. Using C12-200, a gold standard IL, as a model, we designed a library of ILs with varying tail lengths and evaluated their potency in vivo. We demonstrated that small changes in lipophilicity can drastically increase or decrease mRNA translation. We identified that LNPs formulated with firefly luciferase mRNA (1929 base pairs) and C10-200, an IL with shorter tail lengths than C12-200, enhance liver transfection by over 10-fold. Furthermore, different IL tail lengths were found to be ideal for transfection of LNPs encapsulating mRNA cargos of varying sizes. LNPs formulated with erythropoietin (EPO), responsible for stimulating red blood cell production, mRNA (858 base pairs), and the C13-200 IL led to EPO translation at levels similar to the C12-200 LNP. The LNPs formulated with Cas9 mRNA (4521 base pairs) and the C9-200 IL induced over three times the quantity of indels compared with the C12-200 LNP. Our findings suggest that shorter IL tails may lead to higher transfection of LNPs encapsulating larger mRNAs, and that longer IL tails may be more efficacious for delivering smaller mRNA cargos. We envision that the results of this project can be utilized as future design criteria for the next generation of LNP delivery systems for RNA therapeutics.

In situ combinatorial synthesis of degradable branched lipidoids for systemic delivery of mRNA therapeutics and gene editors.

The ionizable lipidoid is a key component of lipid nanoparticles (LNPs). Degradable lipidoids containing extended alkyl branches have received tremendous attention, yet their optimization and investigation are underappreciated. Here, we devise an in situ construction method for the combinatorial synthesis of degradable branched (DB) lipidoids. We find that appending branch tails to inefficacious lipidoids via degradable linkers boosts mRNA delivery efficiency up to three orders of magnitude. Combinatorial screening and systematic investigation of two libraries of DB-lipidoids reveal important structural criteria that govern their in vivo potency. The lead DB-LNP demonstrates robust delivery of mRNA therapeutics and gene editors into the liver. In a diet-induced obese mouse model, we show that repeated administration of DB-LNP encapsulating mRNA encoding human fibroblast growth factor 21 alleviates obesity and fatty liver. Together, we offer a construction strategy for high-throughput and cost-efficient synthesis of DB-lipidoids. This study provides insights into branched lipidoids for efficient mRNA delivery.

High-throughput barcoding of nanoparticles identifies cationic, degradable lipid-like materials for mRNA delivery to the lungs in female preclinical models.

Lipid nanoparticles for delivering mRNA therapeutics hold immense promise for the treatment of a wide range of lung-associated diseases. However, the lack of effective methodologies capable of identifying the pulmonary delivery profile of chemically distinct lipid libraries poses a significant obstacle to the advancement of mRNA therapeutics. Here we report the implementation of a barcoded high-throughput screening system as a means to identify the lung-targeting efficacy of cationic, degradable lipid-like materials. We combinatorially synthesize 180 cationic, degradable lipids which are initially screened in vitro. We then use barcoding technology to quantify how the selected 96 distinct lipid nanoparticles deliver DNA barcodes in vivo. The top-performing nanoparticle formulation delivering Cas9-based genetic editors exhibits therapeutic potential for antiangiogenic cancer therapy within a lung tumor model in female mice. These data demonstrate that employing high-throughput barcoding technology as a screening tool for identifying nanoparticles with lung tropism holds potential for the development of next-generation extrahepatic delivery platforms.

Fast and facile synthesis of amidine-incorporated degradable lipids for versatile mRNA delivery in vivo.

Lipid nanoparticles (LNPs) are widely used for mRNA delivery, with cationic lipids greatly affecting biodistribution, cellular uptake, endosomal escape and transfection efficiency. However, the laborious synthesis of cationic lipids limits the discovery of efficacious candidates and slows down scale-up manufacturing. Here we develop a one-pot, tandem multi-component reaction based on the rationally designed amine-thiol-acrylate conjugation, which enables fast (1 h) and facile room-temperature synthesis of amidine-incorporated degradable (AID) lipids. Structure-activity relationship analysis of a combinatorial library of 100 chemically diverse AID-lipids leads to the identification of a tail-like amine-ring-alkyl aniline that generally affords efficacious lipids. Experimental and theoretical studies show that the embedded bulky benzene ring can enhance endosomal escape and mRNA delivery by enabling the lipid to adopt a more conical shape. The lead AID-lipid can not only mediate local delivery of mRNA vaccines and systemic delivery of mRNA therapeutics, but can also alter the tropism of liver-tropic LNPs to selectively deliver gene editors to the lung and mRNA vaccines to the spleen.

Fabrication of a magnet-assisted alignment device for the amperometric detection of capillary electrophoresis using a carbon nanotube/polypropylene composite electrode.

A magnet-assisted alignment device was designed and fabricated for the amperometric detection of CE. It mainly consisted of a magnet-containing electrode holder, a capillary-based microdisc detection electrode, a detection cell, and a micrometer adjuster. To demonstrate the feasibility and performance of the alignment device, it was used in combination with a carbon nanotube/polypropylene (CNT/PP) composite electrode for the determination of p-phenylenediamine, m-aminophenol, and m-dihydroxybenzene in commercial hair dye by CE. The CNT-based electrode was fabricated by packing a melt mixture of CNTs and PP in a piece of fused silica capillary under heat, offering significantly lower operating potentials, substantially enhanced signal-to-noise characteristics, and high resistance to surface fouling. Because magnetic force was employed to move the detection electrode, the alignment system was significantly simplified. It is characterized by simple design and fabrication, high alignment reproducibility, reduced alignment time, and low cost. Both the alignment device and the CNT/PP composite electrode should find a wide range of applications in microchip CE, flowing injection analysis, and other microfluidic analysis systems.

Emerging nanotechnological approaches to regulating tumor vasculature for cancer therapy.

Abnormal angiogenesis stands for one of the most striking manifestations of malignant tumor. The pathologically and structurally abnormal tumor vasculature facilitates a hostile tumor microenvironment, providing an ideal refuge exclusively for cancer cells. The emergence of vascular regulation drugs has introduced a distinctive class of therapeutics capable of influencing nutrition supply and drug delivery efficacy without the need to penetrate a series of physical barriers to reach tumor cells. Nanomedicines have been further developed for more precise regulation of tumor vasculature with the capacity of co-delivering multiple active pharmaceutical ingredients, which overall reduces the systemic toxicity and boosts the therapeutic efficacy of free drugs. Additionally, precise structure design enables the integration of specific functional motifs, such as surface-targeting ligands, droppable shells, degradable framework, or stimuli-responsive components into nanomedicines, which can improve tissue-specific accumulation, enhance tissue penetration, and realize the controlled and stimulus-triggered release of the loaded cargo. This review describes the morphological and functional characteristics of tumor blood vessels and summarizes the pivotal molecular targets commonly used in nanomedicine design, and then highlights the recent cutting-edge advancements utilizing nanotechnologies for precise regulation of tumor vasculature. Finally, the challenges and future directions of this field are discussed.

The adsorption mechanism of sludge-based biochar toward highly concentrated organic membrane concentrates from landfill leachate.

In this study, the sludge-based biochar (BC) was prepared by dewatered sludge from a membrane bioreactor to treat the membrane concentrate. Then, the adsorbed and saturated BC was regenerated (RBC) by pyrolysis and deashing treatment to further treat the membrane concentrate. Afterward, the composition of membrane concentrate before and after BC or RBC treatment was detected, and the biochars' surface characteristics were characterized. The results showed that RBC outperformed BC in the abatement of chemical oxygen demand (CODCr), ammonia nitrogen (NH3-N), and total nitrogen (TN), with their removal rates of 60.07%, 51.55%, and 66.00%, respectively, an improvement of 9.49%, 9.00% and 16.50% of the removal rate compare to BC. The specific surface area of BC and RBC was about 109 times as much as the original dewatered sludge, and the pore size of BC and RBC belonged to mesopore which was a benefit for removing small and mediate size pollutants. The increase of the oxygen-containing functional group in RBC and the ash abatement contributed much to the improvement of RBC adsorption performance. In addition, cost analysis showed that BC+RBC had a cost of 0.76$/kg for COD removal, which was a lower cost than other common membrane concentrate treatment technologies.

Synergistic phototherapy of NIR wavelength xanthene-quinoline salt-based heavy-atom-free photosensitizers for tumor therapy.

We propose a practical strategy to design a series of heavy-atom-free synergistic phototherapy agents (CSQs) with both photodynamic therapy (PDT) and photothermal therapy (PTT) under NIR wavelength excitation by simply replacing the indole salt of xanthene Changsha (CS) with quinoline salt.

Probiotic-Inspired Nanomedicine Restores Intestinal Homeostasis in Colitis by Regulating Redox Balance, Immune Responses, and the Gut Microbiome.

Microbiota-based therapeutics offer innovative strategies to treat inflammatory bowel diseases (IBDs). However, the poor clinical outcome so far and the limited flexibility of the bacterial approach call for improvement. Inspired by the health benefits of probiotics in alleviating symptoms of bowel diseases, bioartificial probiotics are designed to restore the intestinal microenvironment in colitis by regulating redox balance, immune responses, and the gut microbiome. The bioartificial probiotic comprises two components: an E. coli Nissle 1917-derived membrane (EM) as the surface and the biodegradable diselenide-bridged mesoporous silica nanoparticles (SeM) as the core. When orally administered, the probiotic-inspired nanomedicine (SeM@EM) adheres strongly to the mucus layer and restored intestinal redox balance and immune regulation homeostasis in a murine model of acute colitis induced by dextran sodium sulfate. In addition, the respective properties of the EM and SeM synergistically alter the gut microbiome to a favorable state by increasing the bacterial diversity and shifting the microbiome profile to an anti-inflammatory phenotype. This work suggests a safe and effective nanomedicine that can restore intestinal homeostasis for IBDs therapy.