ADVANCED FUNCTIONAL MATERIALS
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2025
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IF 19
Yi Chen,Wei Chen,Yiming Ren,Yanjie Zhang,Zhaoqi Tan,Wenzhe Huang,Xueshan Bai,Liya Yang,Shuyun Liu,Quanyi Guo,Li Teng
Impaired efferocytosis in diabetic wounds contributes to apoptotic cell accumulation, chronic inflammation, and poor healing outcomes. In this study, a multi-hierarchical hydrogel designed to facilitate cellular debridement and initiate a healing process in diabetic wounds is proposed. A reactive oxygen species (ROS)/glucose-responsive hydrogel conjugated with chemokine aptamers is developed that encapsulated mannose-modified lipid nanoparticles (mLNPs) loaded with ADAM17 siRNA (A disintegrin and metalloproteinase 17). This hydrogel enhanced macrophage recruitment by enriching endogenous chemokines. Additionally, it responded to the pathological microenvironment, enabling the dynamic release of mLNPs for targeted siRNA delivery to macrophages. Treatment with ADAM17 siR@mLNPs significantly enhanced macrophage efferocytosis through the MerTK-Rac1 pathway and glycolytic reprogramming, thereby initiating the resolution of inflammation and tissue repair. Finally, in animal models of diabetic wounds, this therapy reduced the apoptotic burden and improved wound healing. In conclusion, macrophage-targeted efferocytosis-reactivation therapy is a promising strategy for the treatment of diabetic wounds.
研究领域:
医学
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生物材料学
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分子生物学
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高影响因子
CELL DEATH AND DIFFERENTIATION
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2026
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IF 13.6
Li Yue,Zhang Zuo,Yao Ran,Jin Xiying,Yong Zan,Song Xuguang,Sun Cai,Xu Zhengqing,Huang Yujin,Ju Wen,He Yuan,Qiao Jianlin,Zeng Lingyu
Myeloablative treatments before bone marrow (BM) transplantation severely disrupt the microvasculature of the BM, and its regeneration precedes and supports hematopoietic regeneration after BM transplantation. Thus, the identification of factors that regulate BM vascular regeneration after an injury could offer a significant therapeutic opportunity to improve hematopoietic regeneration. After myeloablation, the BM cavity is filled with various dying cell-derived products. Here, we show that after transplantation, dying cell-derived products educate macrophages into a proangiogenic state and enhance vascular regeneration in the BM. Mechanistically, dying cell-derived sphingosine-1-phosphate (S1P) primes hypoxia-inducible factor-1α (HIF-1α) gene expression in macrophages. Importantly, our results revealed that the degradation of apoptotic bodies (ApoBDs) elevates intracellular cholesterol levels and activates their sensor, liver X receptor α (LXRα), in macrophages. Activated LXRα physically binds to the HIF-1α protein and inhibits its ubiquitylation, further potentiating VEGFA expression in macrophages. In vivo studies using transgenic mouse models and liposome-mediated delivery confirm that the LXRα/HIF-1α axis is required for macrophage-driven vascular repair following transplantation. These data not only uncover a new role for macrophages in BM vascular regeneration, but also provide novel evidence demonstrating the unexpected beneficial effect of efferocytosis in eliciting the pro-healing functions of macrophages in the context of injury.
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PubMed
高影响因子
Advanced Healthcare Materials
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2024
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IF 10
Zhiwei Huang,Xinze Li,Dedong Yu,Hengcai Wang,Changju Chun,Yingzheng Zhao
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.
研究领域:
纳米医学
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药理学
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肺科学
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免疫学
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生物材料
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PubMed
高影响因子
Advanced Science
·
2026
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IF 14.1
Zeng Wang,Lai Wei,Mingyang Wang,Shanjie Wang,Lili Xiu,Jiaxiang Sun,Rongzhe Lu,Yige Liu,Jiaxin Wang,Fengyi Liu,Weike Liu,Bo Yu,Yong Sun,Xueqin Gao,Shaohong Fang
Delayed neutrophil clearance after myocardial infarction (MI) significantly disrupts the myocardial microenvironment, but the underlying mechanisms remain unclear. Macrophage-mediated efferocytosis of infiltrating neutrophils is crucial for resolving inflammation and restoring homeostasis post-MI. However, the specific regulatory mechanisms governing neutrophil clearance and efferocytosis remain undefined. This study demonstrates a significant correlation between increased IRGM expression in peripheral blood neutrophils of patients with MI and improved prognostic outcomes. Neutrophil-specific deletion of Irgm1 exacerbates cardiac dysfunction, impairs post-MI repair, and hinders neutrophil clearance and efferocytosis. Irgm1 deficiency further delays neutrophil clearance in the heart and extends neutrophil survival. Mechanistically, Irgm1 directly interacts with PDIA3, promoting its autophagic degradation, which in turn activates the endoplasmic reticulum stress/NF-κB/caspase-3 pathway to facilitate neutrophil clearance and efferocytosis. In vivo administration of LOC14 significantly reduces tissue damage and enhances cardiac recovery in neutrophil Irgm1-deficient mice post-MI. These findings highlight the pivotal role of the Irgm1-PDIA3 axis in facilitating cardiac repair post-MI by promoting neutrophil clearance. LOC14 may serve as a potential therapeutic agent to enhance cardiac function post-MI, particularly in Irgm1-deficient cases.
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高影响因子
JOURNAL OF CONTROLLED RELEASE
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2026
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IF 12.4
Xi Yang,Bolin Li,Wei Li,Zirui Wang,Kexuan Zhao,Zhonghao Hu,Yahan Peng,Tongtong Yang,Chenbing Wang
Impaired macrophage efferocytosis is a major barrier to timely inflammatory resolution in chronic diabetic wounds. We developed an aligned core-shell gelatin/chitosan dressing for local delivery of losmapimod, a p38 MAPK inhibitor, and achieved a controlled, time-decreasing release profile while preserving wet-state structural integrity. In vitro, losmapimod upregulated ANXA1 and enhanced both macrophage efferocytosis and phagocytic activity. In db/db wounds, the losmapimod-loaded scaffold accelerated healing and improved multiple histological features of pro-healing remodeling, including reduced fibrotic signaling, enhanced vascularization, increased epithelial progenitor-associated signals, and more mature collagen organization. Transcriptomic analysis further supported attenuation of inflammatory recruitment-associated programs together with enrichment of epidermal repair-related pathways. Gain- and loss-of-function studies in macrophages, together with in vivo pharmacological modulation, implicated ANXA1-related signaling as an important contributor to these effects. Together, these findings support a local, time-programmed pro-resolution biomaterial strategy for diabetic wound repair and identify macrophage clearance-associated remodeling as a relevant therapeutic axis.
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
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IF 8.2
Zhipeng Li,Wenyu Wang,Liping Zhu,Zhiqiang Wang,Chaolong Liu,Yong Sun,Jingliang Wu,Qing Wang
Diabetic retinopathy (DR), as the most common microvascular complication of diabetes, seriously threatens the vision of diabetic patients. As the resident phagocytes of the retina, microglia participate in inflammation, neovascularization, and neurodegeneration of DR. Herein, apoptotic retinal cell membrane-coated, rapamycin-loaded mesoporous Prussian blue NPs as immunomodulators for ameliorating DR by modulating microglial polarization are reported. The apoM@mPB@Ra NPs exhibited favorable stability and biocompatibility and achieved active targeted delivery due to the specific recognition between “eat me” signal expressed on apoptotic membrane and microglia. In an LPS-induced cellular inflammation model, apoM@mPB@Ra NPs effectively promoted microglial polarization toward the anti-inflammatory phenotype (M2) by scavenging intracellular reactive oxygen species (ROS) combined with affecting the mTOR signaling pathway, leading to downregulation of pro-inflammatory cytokines IL-6 and TNF-α. Meanwhile, owing to the multienzyme-like activities of mPB in nanoparticles, apoM@mPB@Ra NPs obviously alleviated cellular hypoxia, thereby decreasing the expression of VEGF. Notably, in a mouse model of DR, intravitreally injected apoM@mPB@Ra NPs significantly improved the severity of the abnormal retinal vascular network and inflammatory microenvironment of retinopathy by down-regulating the expression of HIF-1α, VEGF, and inflammatory-related cytokines. Collectively, these findings demonstrate that apoM@mPB@Ra NPs provide a promising and effective approach for the treatment of DR.
研究领域:
医学
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药学
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生物材料学
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DOI
PubMed
高影响因子
Nature Communications
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2026
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IF 18.1
Wang Zihao,Cheng Quhan,Zhou Mengxue,Feng Kexin,Chen Qi,Yuan Yi,Zhang Shengmin,Kong Deling,Wang Kai,Wang Jianglin
Erythrocytes and erythrocyte membrane vesicles have shown promise for personalized drug delivery through passive immune evasion, yet their active role in immune phagocytosis remains largely unexplored. Here, we introduce a paradigm based on phosphatidylserine-everted erythrocyte membrane vesicles that trigger efferocytosis, enabling immune-mediated tissue regeneration rather than immune evasion. Incorporation of these phosphatidylserine-everted erythrocyte membrane vesicles into small-diameter vascular grafts markedly enhances endothelialization, suppresses calcification, and improves long-term patency in a rabbit carotid artery replacement model. Preclinical evaluation in a large canine model further demonstrates superior performance compared with clinically used expanded polytetrafluoroethylene grafts. This study establishes engineered phosphatidylserine-everted erythrocyte membrane vesicles as a versatile, customizable, and cost-effective biointerface for vascular grafts and other blood-contacting devices, providing a compelling strategy to harness innate immune mechanisms for regenerative medicine.
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DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2022
·Vol. 32
·期 52
·2207637
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IF 19.924
Hongbin Yang,Zhenyan Yu,Shuaishuai Ji,Jie Yan,Yan kong,Qiang Huo,Zhijun Zhang,Yimin Niu,Yang Liu
The progression of osteoarthritis is associated with chronic synovitis caused by synovial macrophage infiltration and proinflammatory M1 polarization. Accordingly, repolarization of macrophages from the M1 to M2 phenotype by nanoagents is proposed as a potential treatment strategy. However, achieving adequate effects using intra-articular injected agents is challenging due to the rapid drug clearance from the joint space and poor efficiency of nanoparticles endocytosis by synovial macrophage cells. Herein, apoptotic chondrocyte membrane-coated, quercetin-loaded metal-organic framework nanoparticles as immunomodulators for treating osteoarthritis are reported. The apoptotic chondrocyte membrane-camouflaged nanoparticles containing various natural “eat me” signals can be easily disguised as chondrocyte apoptotic bodies in the joints, and thus are more easily phagocytized by synovial macrophages similarly to efferocytosis. Furthermore, the released quercetin promotes the polarization of synovial macrophages to the M2 phenotype and also inhibites the apoptosis of articular chondrocytes. In vivo results suggest that such a “Trojan horse” strategy can extend the retention time of nanoparticles in osteoarthritis joints and improve treatment efficacy. Collectively, it is hoped that this study can offer a potential and universal platform for engineered cell membrane-coated nanoparticles to resolve inflammation by simulating specific inflammatory processes.
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高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
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2025
·Vol. 23
·期 1
·737
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IF 12.6
Zheng Shuting,Zheng Yinfei,Hu Honglei,Liu Minyi,He Chenxi,Wu Zede,Hou Meirong,Liu Guoqiang,Xu Yikai,Yan Chenggong,Zhao Bingxia
Background The efficacy of radiotherapy (RT) is often compromised by tumor radioresistance and an immunosuppressive microenvironment. Two key limitations are the clearance of apoptotic cells (efferocytosis), which can promote an immunosuppressive phenotype, and the acidic tumor microenvironment (TME) that further restrains antitumor immunity. An ideal radiosensitizer should not only enhance radiation-induced cell death but also address these immunological barriers to unlock robust systemic antitumor immunity. Methods We constructed a multifunctional nano-system based on mesoporous organosilicon (HMON) as a template. Leveraging the tunability of the -Si-O-Si- framework, we incorporated manganese (Mn) and calcium (Ca) elements to form a unique –Si–O–M– hybrid structure (M = Mn or Ca). This composite was subsequently loaded with Omeprazole sodium (PPI) and efferocytosis inhibitor, and the surface was modified with hyaluronic acid (HA) for active targeting. In vitro, the radiosensitizing mechanism was investigated in 4T1 cells via western blot, immunofluorescence and flow cytometry. In vivo efficacy was evaluated in 4T1 tumor-bearing BALB/c mice following combined nano-system and RT treatment. Results The resulting nano-system exhibited a high T1 relaxivity (r1 = 8.95 mM⁻¹s⁻¹). In vitro and in vivo studies demonstrated that it significantly enhanced radiation-induced oxidative stress and mitochondrial dysfunction. The combination therapy achieved a remarkable ~ 96% tumor growth inhibition in 4T1 tumor-bearing mice. Crucially, it potentiated immunogenic cell death and activated the cGAS-STING pathway, evidenced by a > 3-fold increase in mature dendritic cells (DCs) and a > 4-fold enhancement in tumor-infiltrating cytotoxic T lymphocytes. Conclusion This study presents a novel “ion-interference amplifier” strategy that concurrently enhances radiosensitization and immune response, offering a powerful model for synergistic radio-immunotherapy. Meanwhile, the integration of MRI-based tracking further underscores its potential for clinical translation. Graphical
研究领域:
纳米医学
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放射肿瘤学
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癌症免疫治疗
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生物医学工程
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分子影像学
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PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2026
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IF 13.2
Xiong Liu,Guangxia Feng,Yuan Ping,Zhiping Zhang,Li Kong
Acute respiratory distress syndrome (ARDS) is a life-threatening respiratory disorder characterized by uncontrolled lung inflammation and diffuse alveolar injury. The impaired macrophage efferocytosis represents a critical pathological mechanism obstructing inflammation resolution in ARDS. In this work, we developed an inhalable engineered apoptotic neutrophil-derived nanovesicle system (TA-Ce/NV) to remodel the lung inflammatory microenvironment by enhancing macrophage efferocytosis. By constructing a polyphenol-metal network protective layer on the surface of nanovesicles through the coordination of tannic acid and cerium ions, this strategy integrates dual functionalities: (1) enhancing nebulization stability of the nanovesicles to overcome limitations in nebulized delivery, and (2) synergizing the immunomodulatory effects of apoptotic vesicles with the reactive oxygen species-scavenging properties to activate macrophage continual efferocytosis. Following nebulized inhalation, TA-Ce/NV demonstrated prolonged retention in inflamed lungs and achieved deep lung deposition. TA-Ce/NV effectively alleviated lung inflammation and promoted tissue repair by activating endogenous repair mechanisms. Additionally, by surface adsorption of the anti-inflammatory cytokine IL-10, TA-Ce/NV served not only as a therapeutic entity but also as a delivery vehicle, providing an innovative therapeutic strategy for ARDS while establishing a novel inhaled delivery platform for pulmonary diseases.
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高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
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IF 13.2
Yu Wang,Teng Wang,Tianze Jiang,Bingjie Wang,Yanguo Su,Tiantian Gan,Xia Zhao
In situ cancer vaccines are a more promising immunotherapeutic strategy than traditional cancer vaccines. However, its clinical application is hindered by insufficient exposure and presentation of tumor-associated antigens (TAAs). Here, we report a co-delivery hydrogel (CCFA@Gel) based on autophagy and efferocytosis as a “cancer vaccine factory” to enhance tumor immunotherapy. CCFA@Gel is a temperature-sensitive hydrogel composed of fucoidan (Fuc)-coated chlorin e6 (Ce6)-chloroquine (CQ) self-assembly and apocynin (APO). After CCFA@Gel targeting tumor cells through the affinity of Fuc to P-selectin, Ce6 induces immunogenic cell death (ICD) by photodynamic therapy (PDT) to trigger the exposure of TAAs. CQ enhances the retention of TAAs by inhibiting autophagy, while APO enhances the presentation of TAAs by inhibiting the efferocytosis of tumor-associated macrophages (TAMs). In vivo results show that CCFA@Gel significantly inhibits primary tumors, as well as tumor metastasis and recurrence by enhancing the exposure, retention and presentation of TAAs. Our study provides a novel strategy for in situ vaccines development to enhance cancer immunotherapy.
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高影响因子
Journal of Advanced Research
·
2024
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IF 11.4
Dongwei Guan,Pengju Huang,Xinlei Liu,Qing Li,Xiaoxun Zhang,Nan Liu,Yong Wang,Ying Wan,Jin Chai,Shiying Cai,Rui Chen,Zhijia Ye
Introduction Niemann-Pick C1 (NPC1), a lysosomal cholesterol transport protein, is required for efficient efferocytosis. Patients with Npc1 mutation are frequently accompanied with hepatic symptoms, including hepatomegaly, elevated liver transaminases, or even acute liver failure, but the pathogenic mechanism remains unknown. Objectives Our work aims to characterize the functional role of myeloid NPC1 in liver injury and elucidate its underlying mechanism. Methods Analyses of injured livers from patients with liver diseases and mouse models were conducted to examine NPC1 expression. Myeloid cell-specific Npc1 knockout mice were constructed to determine the functional role of macrophage NPC1 in liver injury. Isolated macrophages were subjected to in vitro mechanistical assays. Results We found that NPC1 is mainly expressed in hepatic macrophages. Its mRNA and protein expression are significantly elevated in injured livers from both patients and mouse models. Tissue-specific deletion of myeloid Npc1 increased liver inflammation, levels of serum liver function enzymes, and liver fibrosis in mouse models of liver injury induced by carbon tetrachloride (CCl 4 ) injection and methionine-and-choline-deficient (MCD) diets. Further analyses indicate that Npc1 deficiency in mouse models of liver injury resulted in increased levels of serum HMGB1 and mitochondrial DNA, promoted hepatic macrophage proinflammatory activation, M1 polarization, led to overproduction of hepatic inflammatory cytokines/chemokines, e.g. CCL2 and STING/NFκB pathway activation. In vitro mechanistical studies reveal that Npc1 -deficient macrophages exhibited inefficient efferocytosis, partly due to impaired cargo degradation. Conclusions These findings indicate that elevated expression of myeloid NPC1 in liver diseases protects liver from injury by promoting macrophage efferocytosis of damaged cells. Dysfunction of NPC1 aggravates liver injury, suggesting that NPC1 may be a potential therapeutic target for treating liver diseases.
研究领域:
肝病学
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免疫学
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细胞生物学
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病理学
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DOI
PubMed
高影响因子
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