Red Blood Cell Membrane-Coated Nanoparticles Enable Incompatible Blood Transfusions.

Blood transfusions save lives and improve health every day. Despite the matching of blood types being stricter than it ever has been, emergency transfusions among incompatible blood types are still inevitable in the clinic when there is a lack of acceptable blood types for recipients. Here to overcome this, a counter measure nanoplatform consisting of a polymeric core coated by a red blood cell (RBC) membrane is developed. With A-type or B-type RBC membrane camouflaging, the nanoplatform is capable of specifically capturing anti-A or anti-B IgM antibodies within B-type or A-type whole blood, thereby decreasing the corresponding IgM antibody levels and then allowing the incompatible blood transfusions. In addition to IgM, the anti-RBC IgG antibody in a passive immunization murine model can likewise be neutralized by this nanoplatform, leading to prolonged circulation time of incompatible donor RBCs. Noteworthily, nanoplatform made by expired RBCs (>42 days stored hypothermically) and then subjected to lyophilization does not impair their effect on antibody neutralization. Most importantly, antibody-captured RBC-NP do not exacerbate the risk of inflammation, complement activation, and coagulopathy in an acute hemorrhagic shock murine model. Overall, this biomimetic nanoplatform can safely neutralize the antibody to enable incompatible blood transfusion.

Hydrogel-forming viscous liquid in response to ROS restores the gut mucosal barrier of colitis mice via regulating oxidative redox homeostasis.

The disrupted oxidative redox homeostasis plays a critical role in the progress of ulcerative colitis (UC). Herein, hydrogel-forming viscous liquid (HSD) composed of cysteamine-grafted hyaluronic acid (HS) and superoxide dismutase (SOD) has been designed for UC. When the viscous HSD liquid was infused into colitis colon, SOD would convert the pathological superoxide (O2·-) to hydrogen peroxides (H2O2), which was subsequently scavenged by HS. Accordingly, the sol-gel transition of HSD was initiated by scavenging H2O2, enhancing its adhesion toward colitis colon. H2O2-treated HSD presented the higher storage modulus and stronger adhesion force toward porcine colon than the untreated HSD. Besides, H2O2-treated HSD presented the slower erosion profile in the colitis-mimicking medium (pH 3-5), while its rapid degradation was displayed in physiologic condition (pH7.4). The combination of pH-resistant erosion and ROS-responsive adhesion for HSD rendered it with the specifical retention on the inflamed colonic mucosa of DSS-induced colitis mice. Rectally administrating HSD could effectively hinder the body weight loss, reduce the disease activity index and improve the colonic shorting of DSS-induced colitis mice. Moreover, the pro-inflammatory cytokines (IL-1ß, IL-6 and TNF-α) were substantially decreased, the colonic epitheliums were well rearranged and the tight junction proteins were greatly recovered after HSD treatment. Besides, HSD also modulated the gut flora, markedly augmenting the abundance of Firmicutes, Barnesiella and Lachnospiraceae. Moreover, HSD treatment could regulate oxidative redox homeostasis via activating Nrf2-HO-1 pathway to reduce ROS and malondialdehyde and upregulate antioxidant enzymes (SOD, GPx and GSH). Collectively, HSD might be a promising therapy for UC treatments. STATEMENT OF SIGNIFICANCE: Herein, a hydrogel-forming viscous liquid (HSD) was designed by cysteamine-grafted hyaluronic acid (HS) and superoxide dismutase (SOD) for UC treatments. When the viscous HSD liquid was infused into a colitis colon, SOD would convert the pathological superoxide to hydrogen peroxides (H2O2), which was subsequently scavenged by HS. Accordingly, the sol-gel transition of HSD was initiated by scavenging H2O2, enhancing its adhesion to the colitis colon. The colonic epitheliums of DSS-induced colitis mice were well rearranged and the tight junction proteins (Zonula-1 and Claudin-5) were greatly recovered after the HSD treatment. Moreover, the HSD treatment could regulate oxidative redox homeostasis via activating the Nrf2-HO-1 pathway to reduce ROS and malondialdehyde and upregulate antioxidant enzymes (SOD, GPx and GSH).

Opsonization Inveigles Macrophages Engulfing Carrier-Free Bilirubin/JPH203 Nanoparticles to Suppress Inflammation for Osteoarthritis Therapy.

Osteoarthritis (OA) is a chronic inflammatory disease characterized by cartilage destruction, synovitis, and osteophyte formation. Disease-modifying treatments for OA are currently lacking. Because inflammation mediated by an imbalance of M1/M2 macrophages in the synovial cavities contributes to OA progression, regulating the M1 to M2 polarization of macrophages can be a potential therapeutic strategy. Basing on the inherent immune mechanism and pathological environment of OA, an immunoglobulin G-conjugated bilirubin/JPH203 self-assembled nanoparticle (IgG/BRJ) is developed, and its therapeutic potential for OA is evaluated. After intra-articular administration, IgG conjugation facilitates the recognition and engulfment of nanoparticles by the M1 macrophages. The internalized nanoparticles disassemble in response to the increased oxidative stress, and the released bilirubin (BR) and JPH203 scavenge reactive oxygen species (ROS), inhibit the nuclear factor kappa-B pathway, and suppress the activated mammalian target of rapamycin pathway, result in the repolarization of macrophages and enhance M2/M1 ratios. Suppression of the inflammatory environment by IgG/BRJ promotes cartilage protection and repair in an OA rat model, thereby improving therapeutic outcomes. This strategy of opsonization involving M1 macrophages to engulf carrier-free BR/JPH203 nanoparticles to suppress inflammation for OA therapy holds great potential for OA intervention and treatment.

A strategy for oral delivery of FGF21 for mitigating inflammation and multi-organ damage in sepsis.

Fibroblast growth factor 21 (FGF21) shows great therapeutic potential in metabolic, neurodegenerative and inflammatory diseases. However, current FGF21 administration predominantly relies on injection rather than oral ingestion due to its limited stability and activity post-gastrointestinal transit, thereby hindering its clinical utility. Milk-derived exosomes (mEx) have emerged as a promising vehicle for oral drug delivery due to their ability to maintain structural integrity in the gastrointestinal milieu. To address the challenge associated with oral delivery of FGF21, we encapsulated FGF21 within mEx (mEx@FGF21) to protect its activity post-oral administration. Additionally, we modified the surface of mEx@FGF21 by introducing transferrin (TF) to enhance intestinal absorption and transport, designated TF-mEx@FGF21. In vitro results demonstrated that the surface modification of TF promoted FGF21 internalization by intestinal epithelial cells. Orally administered TF-mEx@FGF21 showed promising therapeutic effects in septic mice. This study represents a practicable strategy for advancing the clinical application of oral FGF21 delivery.

BV2 Membrane-Coated PEGylated-Liposomes Delivered hFGF21 to Cortical and Hippocampal Microglia for Alzheimer's Disease Therapy.

Microglia-mediated inflammation is involved in the pathogenesis of Alzheimer's disease (AD), whereas human fibroblast growth factor 21 (hFGF21) has demonstrated the ability to regulate microglia activation in Parkinson's disease, indicating a potential therapeutic role in AD. However, challenges such as aggregation, rapid inactivation, and the blood-brain barrier hinder its effectiveness in treating AD. This study develops targeted delivery of hFGF21 to activated microglia using BV2 cell membrane-coated PEGylated liposomes (hFGF21@BCM-LIP), preserving the bioactivity of hFGF21. In vitro, hFGF21@BCM-LIP specifically targets Aß1-42-induced BV2 cells, with uptake hindered by anti-VCAM-1 antibody, indicating the importance of VCAM-1 and integrin α4/ß1 interaction in targeted delivery to BV2 cells. In vivo, following subcutaneous injection near the lymph nodes of the neck, hFGF21@BCM-LIP diffuses into lymph nodes and distributes along the meningeal lymphatic vasculature and brain parenchyma in amyloid-beta (Aß1-42)-induced mice. Furthermore, the administration of hFGF21@BCM-LIP to activated microglia improves cognitive deficits caused by Aß1-42 and reduces levels of tau, p-Tau, and BACE1. It also decreases interleukin-6  (IL-6) and tumor necrosis factor-α (TNF-α) release while increasing interleukin-10 (IL-10) release both in vivo and in vitro. These results indicate that hFGF21@BCM-LIP can be a promising treatment for AD, by effectively crossing the blood-brain barrier and targeting delivery to brain microglia via the neck-meningeal lymphatic vasculature-brain parenchyma pathways.

The inhibition of MARCO by PolyG alleviates pulmonary fibrosis via regulating mitochondrial function in a silicotic rat model.

Silicon dioxide (SiO2)-induced pulmonary fibrosis is potentially associated with the impairment of mitochondrial function. Previous research found that inhibition of macrophage receptor with collagenous structure (MARCO) could alleviate particle-induced lung injury by regulating phagocytosis and mitigating mitochondrial damage. The present study aims to explore the underlying anti-fibrosis mechanism of polyguanylic acid (PolyG, MARCO inhibitor) in a silicotic rat model. Hematoxylin and eosin and Masson staining were performed to visualize lung tissue pathological changes. Confocal microscopy, transmission electron microscope, western blot analysis, quantitative real-time PCR (qPCR), and adenosine triphosphate (ATP) content assay were performed to evaluate collagen content, mitochondrial function, and morphology changes in SiO2-induced rat pulmonary fibrosis. The results suggested that SiO2 exposure contributed to reactive oxygen species aggregation and the reduction of respiratory complexes and ATP synthesis. PolyG treatment could effectively reduce MARCO expression and ameliorate lung injury and fibrosis by rectifying the imbalance of mitochondrial respiration and energy synthesis. Furthermore, PolyG could maintain mitochondrial homeostasis by promoting peroxisome proliferator-activated receptor-coactivator 1 α (PGC1α)-mediated mitochondrial biogenesis and regulating fusion and fission. Together, PolyG could ameliorate SiO2-induced pulmonary fibrosis via inhibiting MARCO to protect mitochondrial function.

Efferocytosis-Inspired Biomimetic Nanoplatform for Targeted Acute Lung Injury Therapy.

Acute lung injury (ALI) is a serious inflammatory disease that causes impairment of pulmonary function. Phenotypic modulation of macrophage in the lung using fibroblast growth factor 21 (FGF21) may be a potential strategy to alleviate lung inflammation. Consequently, achieving specific delivery of FGF21 to the inflamed lung and subsequent efficient FGF21 internalization by macrophages within the lung becomes critical for effective ALI treatment. Here, an apoptotic cell membrane-coated zirconium-based metal-organic framework UiO-66 is reported for precise pulmonary delivery of FGF21 (ACM@U-FGF21) whose design is inspired by the process of efferocytosis. ACM@U-FGF21 with apoptotic signals is recognized and internalized by phagocytes in the blood and macrophages in the lung, and then the intracellular ACM@U-FGF21 can inhibit the excessive secretion of pro-inflammatory cytokines by these cells to relieve the inflammation. Utilizing the homologous targeting properties inherited from the source cells and the spontaneous recruitment of immune cells to inflammatory sites, ACM@U-FGF21 can accumulate preferentially in the lung after injection. The results prove that ACM@U-FGF21 effectively reduces inflammatory damage to the lung by modulating lung macrophage polarization and suppressing the excessive secretion of pro-inflammatory cytokines by activated immune cells. This study demonstrates the usefulness of efferocytosis-inspired ACM@U-FGF21 in the treatment of ALI.

Biomaterial-assisted strategies to improve islet graft revascularization and transplant outcomes.

Islet transplantation holds significant promise as a curative approach for type 1 diabetes (T1D). However, the transition of islet transplantation from the experimental phase to widespread clinical implementation has not occurred yet. One major hurdle in this field is the challenge of insufficient vascularization and subsequent early loss of transplanted islets, especially in non-intraportal transplantation sites. The establishment of a fully functional vascular system following transplantation is crucial for the survival and secretion function of islet grafts. This vascular network not only ensures the delivery of oxygen and nutrients, but also plays a critical role in insulin release and the timely removal of metabolic waste from the grafts. This review summarizes recent advances in effective strategies to improve graft revascularization and enhance islet survival. These advancements include the local release and regulation of angiogenic factors (e.g., vascular endothelial growth factor, VEGF), co-transplantation of vascular fragments, and pre-vascularization of the graft site. These innovative approaches pave the way for the development of effective islet transplantation therapies for individuals with T1D.

P407 hydrogel loaded with nitric oxide microbubbles promotes angiogenesis and functional improvement in testicular transplantation.

Prepubertal male patients with cancer have decreased fertility after treatment, but there are currently no suitable means for fertility rescue. Testicular transplantation seems to be a promising treatment. The short-term insufficiency of blood supply after transplantation is the key problem that needs to be solved. In this research, nitric oxide (NO), a gas and small molecule transmitter with the effect of promoting angiogenesis, acted at the site of testicular transplantation. Herein, poloxamer-407 (P407) and lipid microbubble materials served as transport carriers for NO and helped NO to function at the transplant site. P407 hydrogel loaded with NO microbubbles (PNO) slowly released NO in vitro. The three-dimensional space of the hydrogel provided a stable environment for NO microbubbles, which is conducive to the continuous release of NO. In this study, 25% PNO (w/v) was selected, and the gelling temperature was 19.47 °C. The gelling efficiency was relatively high at body temperature. Rheological experiments showed that PNO, at this concentration, had stable mechanical properties. The results from in vivo experiments demonstrated that testicular grafts in the PNO group exhibited a notably accelerated blood flow recovery compared to the other groups. Additionally, the PNO group displayed a significant improvement in reproductive function recovery. In conclusion, PNO exhibited slow release of NO, and a small amount of NO promoted angiogenesis in testicular grafts and restored reproductive function.

Bilirubin/morin self-assembled nanoparticle-engulfed collagen/polyvinyl alcohol hydrogel accelerates chronic diabetic wound healing by modulating inflammation and ameliorating oxidative stress.

Chronic diabetic wounds pose a serious threat to human health and safety because of their refractory nature and high recurrence rates. The formation of refractory wounds is associated with wound microenvironmental factors such as increased expression of proinflammatory factors and oxidative stress. Bilirubin is a potent endogenous antioxidant, and morin is a naturally active substance that possesses anti-inflammatory and antioxidant effects. Both hold the potential for diabetic wound treatment by intervening in pathological processes. In this study, we developed bilirubin/morin-based carrier-free nanoparticles (BMn) to treat chronic diabetic wounds. In vitro studies showed that BMn could effectively scavenge overproduced reactive oxygen species and suppress elevated inflammation, thereby exerting a protective effect. BMn was then loaded into a collagen/polyvinyl alcohol gel (BMn@G) for an in vivo study to maintain a moist environment for the skin and convenient biomedical applications. BMn@G exhibits excellent mechanical properties, water retention capabilities, and in vivo safety. In type I diabetic mice, BMn@G elevated the expression of the anti-inflammatory factor IL-10 and concurrently diminished the expression of the proinflammatory factor TNF-α in the tissues surrounding the wounds. Furthermore, BMn@G efficiently mediated macrophage polarization from the M1-type to the M2-type, thereby fostering anti-inflammatory effects. Additionally, BMn@G facilitated the conversion of type III collagen fiber bundles to type I collagen fiber bundles, resulting in a more mature collagen fiber structure. This study provides a promising therapeutic alternative for diabetic wound healing.

Low Expression of Lipoic Acid Synthase Aggravates Silica-Induced Pulmonary Fibrosis by Inhibiting the Differentiation of Tregs in Mice.

Aims: In addition to reducing the respiratory function, crystalline silica (SiO2) disturbs the immune response by affecting immune cells during the progression of silicosis. Regulatory T cell (Treg) differentiation may play a key role in the abnormal polarization of T helper cell (Th)1 and Th2 cells in the development of silicosis-induced fibrosis. Alpha-lipoic acid (ALA) has immunomodulatory effects by promoting Tregs differentiation. Thus, ALA may have a therapeutic potential for treating autoimmune disorders in patients with silicosis. However, little is known regarding whether ALA regulates the immune system during silicosis development. Results: We found that the expression levels of collagen increased, and the antioxidant capacity was lower in the Lias-/-+SiO2 group than in the Lias+/++SiO2 group. The proportion of Tregs decreased in the peripheral blood and spleen tissue in mice exposed to SiO2. The proportion of Tregs in the Lias-/-+SiO2 group was significantly lower than that in the Lias+/++SiO2 group. Supplementary exogenous ALA attenuates the accumulation of inflammatory cells and extracellular matrix in lung tissues. ALA promotes the immunological balance between Th17 and Treg responses during the development of silicosis-induced fibrosis. Innovation and Conclusion: Our findings confirmed that low expression of lipoic acid synthase aggravates SiO2-induced silicosis, and that supplementary exogenous ALA has therapeutic potential by improving Tregs in silicosis fibrosis.

Overexpression of Lias Gene Alleviates Cadmium-Induced Kidney Injury in Mice Involving Multiple Effects: Metabolism, Oxidative Stress, and Inflammation.

Oxidative stress is an important mechanism underlying toxicity induced by cadmium (Cd) exposure. However, there are significant differences of the antioxidant baseline in different populations. This means that different human has different intensity of oxidative stress in vivo after exposure to toxicants. LiasH/H mouse is a specific model which is created by genetically modifying the Lias 3'-untranslated region (3'-UTR). LiasH/H mice express high levels of LA and have high endogenous antioxidant capacity which is approximately 150% higher than wild-type C57BL/6 J mice (WT, Lias+/+). But more importantly, they have dual roles of metal chelator and antioxidant. Here, we applied this mouse model to evaluate the effect of endogenous antioxidant levels in the body on alleviating Cd-induced renal injury including Cd metabolism, oxidative stress, and inflammation. In the experiment, mice drank water containing Cd (50 mg/L), for 12 weeks. Many biomarkers of Cd metabolism, oxidative stress, inflammation, and major pathological changes in the kidney were examined. The results showed overexpression of the Lias gene decreased Cd burden in the body of mice, mitigated oxidative stress, attenuated the inflammatory response, and subsequent alleviated cadmium-induced kidney injury in mice.

In situ gel-forming oil as rectally delivering platform of hydrophobic therapeutics for ulcerative colitis therapy.

Because of their poor water-soluble properties and non-specific distribution, most hydrophobic therapeutics had limited benefit for patients with ulcerative colitis. Herein, an in-situ oil-based gel has been developed as a rectal delivery vehicle for these therapeutics. In situ gel-forming oil (BBLG) was composed of soybean phosphatidyl choline (40%, w/w), glyceryl dioleate (50%, w/w), and ethanol (10%, w/w). The hydrophobic laquinimod (LAQ) as a model drug was easily dissolved in gel-forming oil and its solubility was reaching to 7 ± 0.1 mg/mL. Importantly, upon contact with the colonic fluids, the gel-forming oil was quickly transited to a semi-solid gel, adhering to the inflamed colon mucosa and forming a protective barrier. Transmission Electron Microscopy showed that the gel network was arranged by the connected lipid spheres and LAQ was non-crystally encapsulated into the lipid spheres. Moreover, the universal adhesive test showed that the adhesive force and the adhesive energy of BBLG toward fresh colon tissues were 711 ± 12 mN and 25 ± 2 J/m2, which was 2.14-fold and 5-fold higher than that of the marketed Poloxamer 407 gel, respectively. Meanwhile, in vivo imaging confirmed that the retention time of BBLG in the colon lumen was more than 8 h after rectal administration. In vivo animal studies showed that BBLG also greatly enhanced the therapeutic impact of LAQ on TNBS-treated rats with ulcerative colitis, as evidenced by reduced disease activity index (DAI) scores and weight loss. Moreover, the colonic inflammation was significantly alleviated and the goblet cells were obliviously restored after treatment. Importantly, the gut mucosa barrier was largely repaired without any formation of fibrosis remodeling. Conclusively, in situ liquid gel may be a potential delivery system of hydrophobic medicines for ulcerative colitis.

Lias overexpression alleviates pulmonary injury induced by fine particulate matter in mice.

Oxidative stress and inflammation are mechanisms underlying toxicity induced by fine particulate matter (PM2.5). The antioxidant baseline of the human body modulates the intensity of oxidative stress in vivo. This present study aimed to evaluate the role of endogenous antioxidants in alleviating PM2.5-induced pulmonary injury using a novel mouse model (LiasH/H) with an endogenous antioxidant capacity of approximately 150% of its wild-type counterpart (Lias+/+). LiasH/H and wild-type (Lias+/+) mice were randomly divided into control and PM2.5 exposure groups (n = 10), respectively. Mice in the PM2.5 group and the control group were intratracheally instilled with PM2.5 suspension and saline, respectively, once a day for 7 consecutive days. The metal content, major pathological changes in the lung, and levels of oxidative stress and inflammation biomarkers were examined. The results showed that PM2.5 exposure induced oxidative stress in mice. Overexpression of the Lias gene significantly increased the antioxidant levels and decreased inflammatory responses induced by PM2.5. Further study found that LiasH/H mice exerted their antioxidant function by activating the ROS-p38MAPK-Nrf2 pathway. Therefore, the novel mouse model is useful for the elucidation of the mechanisms of pulmonary injury induced by PM2.5.

Sustained remission of type 2 diabetes in rodents by centrally administered fibroblast growth factor 4.

Type 2 diabetes (T2D) is a major health and economic burden worldwide. Despite the availability of multiple drugs for short-term management, sustained remission of T2D is currently not achievable pharmacologically. Intracerebroventricular administration of fibroblast growth factor 1 (icvFGF1) induces sustained remission in T2D rodents, propelling intense research efforts to understand its mechanism of action. Whether other FGFs possess similar therapeutic benefits is currently unknown. Here, we show that icvFGF4 also elicits a sustained antidiabetic effect in both male db/db mice and diet-induced obese mice by activating FGF receptor 1 (FGFR1) expressed in glucose-sensing neurons within the mediobasal hypothalamus. Specifically, FGF4 excites glucose-excited (GE) neurons while inhibiting glucose-inhibited (GI) neurons. Moreover, icvFGF4 restores the percentage of GI neurons in db/db mice. Importantly, intranasal delivery of FGF4 alleviates hyperglycemia in db/db mice, paving the way for non-invasive therapy. We conclude that icvFGF4 holds significant therapeutic potential for achieving sustained remission of T2D.

Activation of AMPK signalling by Metformin: Implication an important molecular mechanism for protecting against mice silicosis via inhibited endothelial cell-to-mesenchymal transition by regulating oxidative stress and apoptosis.

Inhalation of silica particles (SiO2) causes oxidative stress-induced inflammation and cell apoptosis, ultimately resulting in irreversible pulmonary fibrosis, Unfortunately, effective treatment or preventative measures have yet to be fully established. Metformin (Met), a relatively safe and effective medication for treating diabetes, may hold promise as protective agent against early-stage pulmonary fibrosis in mice through the activation of autophagy and inhibition of endothelial cell to mesenchymal transition (EndoMT). Here, we investigated whether Met could reduce silicosis in mice by regulating inflammation, oxidative stress, and apoptosis, and to identify the underlying protective effect on endothelial cells. First, through pathological observation, we found that 21 consecutive days of Met (100 mg/kg) administration is optimal against silicosis. Next, using haematoxylin-eosin and Masson's trichrome staining and immunoblotting, we found that Met effectively blunted the inflammatory response and collagen deposition at 56 days after exposure to SiO2. We also demonstrated that Met effectively activates AMPK signalling and markedly relieves oxidative stress, the mitochondrial apoptotic pathway and EndoMT induced by SiO2 exposure both in vivo and in vitro. Overall, Met can alleviate SiO2-induced pulmonary fibrosis by regulating oxidative stress and the mitochondrial apoptotic pathway. The current study provides a rationale for the clinical treatment of SiO2-induced pulmonary fibrosis.

Polydopamine-cladded montmorillonite micro-sheets as therapeutic platform repair the gut mucosal barrier of murine colitis through inhibiting oxidative stress.

Montmorillonite (MMT), a layered aluminosilicate, has a mucosal nutrient effect and restores the gut barriers integrity. However, orally administrating MMT is not effective to combat the reactive oxygen species (ROS) and alleviate the acute inflammatory relapse for colitis patients. Herein, polydopamine-doped montmorillonite micro-sheets (PDA/MMT) have been developed as a therapeutic platform for colitis treatment. SEM and EDS analysis showed that dopamine monomer (DA) was easily polymerized in alkaline condition and polydopamine (PDA) was uniformly cladded on the surface of MMT micro-sheets. The depositing amount of PDA was reaching to 2.06 â€‹± â€‹0.08%. Moreover, in vitro fluorescence probes experiments showed that PDA/MMT presented the broad spectra of scavenging various ROS sources including •OH, •O2-, and H2O2. Meanwhile, the intracellular ROS of Rosup/H2O2 treated Caco-2 â€‹cell was also effectively scavenged by PDA/MMT, which resulted in the obvious improvement of the cell viability under oxidative stress. Moreover, most of orally administrated PDA/MMT was transited to the gut and form a protective film on the diseased colon. PDA/MMT exhibited the obvious therapeutic effect on DSS-induced ulcerative colitis mouse. Importantly, the gut mucosa of colitis mouse was well restored after PDA/MMT treatment. Moreover, the colonic inflammation was significantly alleviated and the goblet cells were obliviously recovered. The therapeutic mechanism of PDA/MMT was highly associated with inhibiting oxidative stress. Collectively, PDA/MMT micro-sheets as a therapeutic platform may provide a promising therapeutic strategy for UC treatment.

Doxorubicin Detoxification in Healthy Organs Improves Tolerability to High Drug Doses for Enhanced Antitumor Therapy.

With its well-documented toxicity, the use of doxorubicin (Dox) for cancer treatment requires trade-offs between safety and effectiveness. This limited use of Dox also hinders its functionality as an immunogenic cell death inducer, thus impeding its usefulness for immunotherapeutic applications. Here, we develop a biomimetic pseudonucleus nanoparticle (BPN-KP) by enclosing GC-rich DNA within erythrocyte membrane modified with a peptide to selectively target healthy tissue. By localizing treatment to organs susceptible to Dox-mediated toxicity, BPN-KP acts as a decoy that prevents the drug from intercalating into the nuclei of healthy cells. This results in significantly increased tolerance to Dox, thereby enabling the delivery of high drug doses into tumor tissue without detectable toxicity. By lessening the leukodepletive effects normally associated with chemotherapy, dramatic immune activation within the tumor microenvironment was also observed after treatment. In three different murine tumor models, high-dose Dox with BPN-KP pretreatment resulted in significantly prolonged survival, particularly when combined with immune checkpoint blockade therapy. Overall, this study demonstrates how targeted detoxification using biomimetic nanotechnology can help to unlock the full potential of traditional chemotherapeutics.

Formulation strategies to provide oxygen-release to contrast local hypoxia for transplanted islets.

Islet transplantation refers to the transfusion of healthy islet cells into the diabetic recipients and reconstruction of their endogenous insulin secretion to achieve insulin independence. It is a minimally invasive surgery that holds renewed prospect as a therapeutic method for type 1 diabetes mellitus. However, poor oxygenation in the early post-transplantation period is considered as one of the major causes of islet loss and dysfunction. Due to the metabolism chacteristics, islets required a high supply of oxygen for cell survival while a hypoxia environment would lead to severe islet loss and graft failure. Emerging strategies have been proposed, including providing external oxygen and speeding up revascularization. From the perspective of formulation science, it is feasible and practical to protect transplanted islets by oxygen-release before revascularization as opposed to local hypoxia. In this study, we review the potential formulation strategies that could provide oxygen-release by either delivering external oxygen or triggering localized oxygen generation for transplanted islets.