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ANALYTICAL CHEMISTRY · 2025 · IF 6.7

Ultra-Sensitive Near-Infrared Imaging of Micro-Neuroinflammation with Surface-Engineered Silver Indium Selenide Quantum Dots

Wanru Tian,Xin Zhao,Yao Li,Xuan Cheng,Zheng Yang,Peisen Zhang,Mingxia Jiao,Xiliang Luo

Encephalitis, a severe inflammatory brain condition, poses significant diagnostic challenges due to its heterogeneous symptoms and the limitations of conventional imaging techniques, such as magnetic resonance imaging (MRI), which often fail to detect early or subtle lesions. To address this clinical need, herein, a near-infrared (NIR) optical imaging strategy using engineered silver indium selenide quantum dots (QDs) was developed for precise and early detection of microencephalitic lesions. The QDs were synthesized via a robust aqueous-phase method with optimized NIR emission intensity through suppression of nonradiative recombination pathways. Surface modification with carboxyl-terminated poly(ethylene glycol) (carboxyl-PEG) enhanced colloidal stability, biocompatibility, and selective uptake capabilities by disease-associated M1 macrophages, improving localization at inflammatory sites. In vivo studies demonstrated the outstanding imaging performance of QDs, with encephalitis lesions clearly delineated at ultrahigh spatial resolution, enabling reliable detection of microinflammatory foci as small as 4.6 mm × 5.3 mm. This breakthrough capability facilitates early diagnosis by resolving sub-5 mm lesions, surpassing the sensitivity and resolution of conventional methods for the first time. By providing a noninvasive, high-resolution diagnostic tool, this technology holds potential for improving clinical decision-making and patient outcomes in encephalitis and other neuroinflammatory disorders, particularly in resource-limited settings where early diagnosis remains challenging.

CAS / MDL: 107-21-1 7782-49-2
研究领域: 神经免疫学 · 分子影像学 · 纳米医学 · 转化医学 · 生物材料 · 神经病学 · 炎症生物学
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Food Science and Human Wellness · 2024 · IF 5.6

Sulforaphane ameliorates non-alcoholic steatohepatitis by KLF4-mediated macrophage M2 polarization

Xianghui Huang,Jia Xu,Ye Xu,Bingxin Huangfu,Feng Zhang,Yanzhou Hu,Ruxin Gao,Xinxin Ren,Boyang Zhang,Kunlun Huang,Xiaoyun He

Non-alcoholic fatty liver disease (NAFLD) has become a global issue and a severe threat to public health. However, to date, no approved therapeutic drugs have been developed. Dietary interventions with natural products have shown promise in preventing and treating NAFLD. Sulforaphane (SFN) is a phytocompound with antioxidant and anti-inflammatory properties, and previous research has demonstrated that SFN can ameliorate hepatic lipid accumulation and inflammation. However, the molecular mechanisms underlying these beneficial effects remain unclear. In this study, we confirmed the protective effects of SFN on excessive lipid accumulation and inflammatory injury in a high-fat, high-fructose diet-induced non-alcoholic steatohepatitis (NASH) mouse model. We found that SFN attenuates the inflammatory injury in a macrophage cell line and the liver of NASH mice, owing to the promotion of M1-type macrophage polarization toward the M2-type and the regulation of inflammatory mediators. Further analysis demonstrated that this SFN-induced macrophage M2-type polarization occurs in a Krüppel-like factor 4 (KLF4)-dependent manner. In summary, we uncovered a new mechanism of action underlying SFN activity and provide evidence that dietary intervention with SFN might be protective against NASH.

CAS / MDL: 4478-93-7
研究领域: 肝病学 · 免疫学 · 药理学 · 营养学
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Journal of Ginseng Research · 2025 · IF 5.6

Total saponins of Panax japonicus alleviate adjuvant-induced arthritis in rats by regulating macrophage polarization and intestinal microbiota

Kang Zhou,Huanghe Yu,Huihong Duan,Yupei Yang,Wenbing Sheng,Yixing Qiu,Wei Wang,Bin Li

Background Heightened glycolysis-driven activation of pro-inflammatory M1 macrophages is a characteristic of rheumatoid arthritis (RA). Dysbiosis of the intestinal microbiota is considered a trigger for the immune response in RA. Panax japonicus is used in ethnomedicine to treat RA, but its molecular mechanisms regarding macrophage polarization and the intestinal microbiota remain to be explored. Methods In vitro and in vivo models were established using lipopolysaccharide (LPS)-induced RAW 264.7 macrophage cells and adjuvant-induced arthritis (AIA) rats, and treated with total saponins from Panax japonicus (TSPJ). Inflammatory cytokines were quantified by enzyme-linked immunosorbent assay (ELISA). Glucose, lactate, and LPS were measured by biochemical kits. The M1/M2a ratio in RAW 264.7 cells was assessed by flow cytometry. Joint bone erosion was evaluated by micro-CT. Immunohistochemistry and western blotting were used to evaluate glycolytic regulators in rat joints. Colonic contents and mucosa were analyzed by 16S rRNA sequencing. Results TSPJ inhibited inflammatory response, lactate production, and glucose consumption in M1 macrophages, and restored the M2a/M1 balance. In vivo , TSPJ alleviated joint swelling in AIA rats, reduced serum inflammatory cytokines, lactate, and LPS levels, while increasing anti-inflammatory cytokine levels. The protein expressions of hypoxia-inducible factor-1α (HIF-1α), glucose transporter 1 (GLUT1), hexokina se 2 (HK2), and lactate dehydrogenase A (LDHA) in the ankle joints were down-regulated after TSPJ intervention. Furthermore, TSPJ restored microbiota diversity and community structure, and enriched probiotic abundances like Eubacterium_coprostanoligenes_group and Christensenella . Conclusion TSPJ alleviates arthritis by inhibiting glycolysis pathway in M1 macrophages, modulating colon microbiota, and promoting the abundance of mucosa-associated probiotics.

CAS / MDL: 133073-73-1 154-17-6
研究领域: 药理学 · 免疫学 · 微生物学 · 分子生物学 · 民族药理学 · 风湿病学
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Acta Biomaterialia · 2021 · IF 8.947

Hydrogel-coated needles prevent puncture site bleeding

Shunbo Wei,Yanhua Xu,Zhiwei Wang,Mingxing Li,Peng Sun,Boao Xie,Ying Xing,Hualong Bai,Quancheng Kan,Jiang'an Li,Alan Dardik

Introduction Incomplete hemostasis after vascular cannulation can cause a hematoma or pseudoaneurysm. We hypothesized that a hydrogel-coated needle would effectively and rapidly stop bleeding after vascular cannulation. Methods : A hydrogel composed of sodium alginate , hyaluronic acid , and calcium carbonate was coated onto the surface of suture needles. Needles were observed using scanning electronic microscopy (SEM) and immunofluorescence. Cannulation was performed in both mouse and rat models; the liver, kidney, jugular vein, inferior vena cava and aorta were punctured using uncoated and hydrogel-coated needles. Needles coated with a hydrogel with and without CD34 antibody were used to puncture the rat jugular vein and aorta. Tissues were examined by histology and immunofluorescence. Results : The hydrogel was successfully coated onto the surface of 22G and 30G needles and confirmed by SEM. Hydrogel-coated needles rapidly stopped bleeding after cannulation of the liver, kidney, jugular vein, inferior vena cava and aorta. Hydrogel-coated needles that contained CD34 antibody attracted vascular progenitor cells near the puncture site; there were fewer M1-type macrophages and more M2-type macrophages. Conclusion : Hydrogel-coated needles can effectively and rapidly stop puncture-site bleeding. The hydrogel that contains CD34 antibody attracted vascular progenitor cells, potentially promoting healing of the site after cannulation. Statement of significance Incomplete hemostasis after vascular cannulation can cause a hematoma or pseudoaneurysm and remains a significant clinical problem. We developed a hydrogel composed of sodium alginate, hyaluronic acid, and calcium carbonate; hydrogel-coated needles effectively and rapidly stopped bleeding after vascular cannulation. Interestingly, the hydrogel can also serve as a carrier for drugs that are delivered to the puncture site during the short time of cannulation that could additionally promote puncture site healing. Hydrogel-coated needles may be a new method for rapid hemostasis with application to patients especially at risk for bleeding.

CAS / MDL: 81-88-9
研究领域: 止血 · 血管外科 · 生物医学工程 · 组织工程
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Frontiers in Pharmacology · 2021 · IF 5.811

Anti-inflammatory Activity of a Polypeptide Fraction From Achyranthes bidentate in Amyloid β Oligomers Induced Model of Alzheimer’s Disease

Ge Xiangyu,Wang Yitong,Yu Shu,Cao Xuemin,Chen Yicong,Cheng Qiong,Ding Fei

Neuroinflammation plays a crucial role in neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), and anti-inflammation has been considered as a potential therapeutic strategy. Achyranthes bidentate polypeptide fraction k (ABPPk) was shown to protect neurons from death and suppress microglia and astrocyte activation in PD model mice. However, how ABPPk regulates neuroinflammation to exert a neuroprotective role remains unclear. Toxic Aβ oligomers (AβOs) can trigger inflammatory response and play an important role in the pathogenesis of AD. In the present study, for the first time, we investigated the effects and underlying mechanisms of ABPPk on neuroinflammation in AβOs-induced models of AD. In vitro, ABPPk pretreatment dose-dependently inhibited AβOs-induced pro-inflammatory cytokines mRNA levels in BV2 and primary microglia. ABPPk pretreatment also reduced the neurotoxicity of BV2 microglia-conditioned media on primary hippocampal neurons. Furthermore, ABPPk down-regulated the AβOs-induced phosphorylation of IκBα and NF-κB p65 as well as the expression of NLRP3 in BV2 microglia. In vivo, ABPPk pre-administration significantly improved locomotor activity, alleviated memory deficits, and rescued neuronal degeneration and loss in the hippocampus of AβOs-injected mice. ABPPk inhibited the activation of microglia in hippocampal CA3 region and suppressed the activation of NF-κB as well as the expression of NLRP3, cleaved caspase-1, and ASC in the brain after AβOs injection. ABPPk hindered the release of pro-inflammatory cytokines and promoted the release of anti-inflammatory cytokines in the brain. Notably, the polarization experiment on BV2 microglia demonstrated that ABPPk inhibited M1-phenotype polarization and promoted M2-phenotype polarization by activating the LPS- or AβOs-impaired autophagy in microglia. Taken together, our observations indicate that ABPPk can restore the autophagy of microglia damaged by AβOs, thereby promoting M2-phenotype polarization and inhibiting M1-phenotype polarization, thus playing a role in regulating neuroinflammation and alleviating neurotoxicity.

CAS / MDL: 920-66-1
研究领域: 神经科学 · 药理学 · 炎症 · 神经退行性疾病
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Advanced Healthcare Materials · 2022 ·Vol. 11 ·期 19 ·2200776 · IF 11.092

Functional 2D Iron-Based Nanosheets for Synergistic Immunotherapy, Phototherapy, and Chemotherapy of Tumor

Xingbo Wang,Yan Cheng,Xiaoqing Han,Jiao Yan,Yunyun Wu,Panpan Song,Yanjing Wang,Xi Li,Haiyuan Zhang

Immunotherapy efficacy has been limited by tumor-associated macrophages (TAMs), which are the most abundant immune regulatory cells infiltrating around tumor tissues. The repolarization of pro-tumor M2 TAMs to anti-tumor M1 TAMs is a very promising immunotherapeutic strategy for cancer therapy. In this manuscript, multifunctional 2D iron-based nanosheets (FeNSs) are synthesized via a simple hydrothermal method for the first time, which not only possess photothermal and photodynamic properties, but also can repolarize TAMs from M2 to M1. After modifying with polyethylene glycol and loading with bioreductive prodrug banoxantrone (AQ4N), abbreviated as AP FeNSs, it can effectively repolarize TAMs from M2 to M1 and deliver AQ4N to tumor microenvironment (TME). Moreover, the repolarized M1 TAMs overexpress inducible nitric oxide synthase, which can convert nontoxic AQ4N to cytotoxic AQ4 under hypoxic TME, enabling immunomodulation-activated chemotherapy. A series of in vitro and in vivo results corroborate that AP FeNSs effectively exert photothermal and photodynamic effects and repolarize M2 TAMs to M1 TAMs, releasing inflammatory factors and activating the chemotherapeutic effect, thereby realizing synergistic tumor therapy.

研究领域: 癌症治疗 · 材料科学 · 免疫学 · 纳米医学
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ACS Applied Nano Materials · 2020 · IF 0

C60-Decorated Melanin Nanoparticles Conjugated with Hyaluronic Acid for Synergistic Theranostic and Immunotherapy of Tumors under near-Infrared Excitation

Jia-Hui Yan,Yi-Shun Ji,Man-Li Yang,Jun Fu,Hu Shan,Li−Li Wang,Lei Zhang,Jing-Yuan Xiao,Xiao-Ying Kong,Jin-Sheng Shi

Photodynamic therapy (PDT), a promising noninvasive tumor treatment strategy, is limited by poor biocompatibility, high cost, and complicated synthesis procedures of rare-earth up-conversion materials. Herein, natural melanin particles (MNPs), excellent photothermal therapy (PTT) materials, were found to significantly promote production of reactive oxygen species (ROS) under 808 nm irradiation when cross-linked with C60, whereas synthetic polydopamine had no such property. On the basis of this special character of MNP, MNP-C60-hyaluronic acid (MC60H) nanoparticles, independent of rare-earth up-conversion materials, were prepared for multimodal attack toward a tumor under 808 nm irradiation. After targeting recognition by hyaluronic acid (HA), MC60H could not only efficiently promote temperature rise and the production ROS in tumor but also activate the prominent immunotherapy and help tumor immunosuppressed M2-type macrophages transformed into antitumor M1-type. Under the premise of high biosecurity and simple preparing strategy, the versatile nanoparticle material, MC60H, is utilized for collaborative PTT, PDT, and immunotherapy under NIR excitation without participation of any rare-earth elements. The character of promoting ROS production of C60 by MNP, which is a natural biomaterial, is first reported in this paper, which provides a good demonstration of MC60H in application of a synergistic antitumor strategy without the dependence of traditional up-conversion material.

CAS / MDL: 25952-53-8 6066-82-6
研究领域: 生物医学工程 · 纳米技术 · 癌症治疗 · 材料科学
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Research · 2024 · IF 8.5

Pt–Se Hybrid Nanozymes with Potent Catalytic Activities to Scavenge ROS/RONS and Regulate Macrophage Polarization for Osteoarthritis Therapy

Hong Wei,Hongjun Huang,Haoqiang He,Yuanming Xiao,Lu Chun,Zhiqiang Jin,Hanyang Li,Li Zheng,Jinmin Zhao,Zainen Qin

The activation of pro-inflammatory M1-type macrophages by overexpression of reactive oxygen species (ROS) and reactive nitrogen species (RONS) in synovial membranes contributes to osteoarthritis (OA) progression and cartilage matrix degradation. Here, combing Pt and Se with potent catalytic activities, we developed a hybrid Pt–Se nanozymes as ROS and RONS scavengers to exert synergistic effects for OA therapy. As a result, Pt–Se nanozymes exhibited efficient scavenging effect on ROS and RONS levels, leading to repolarization of M1-type macrophages. Furthermore, the polarization of synovial macrophages to the M2 phenotype inhibited the expression of pro-inflammatory factors and salvaged mitochondrial function in arthritic chondrocytes. In vivo results also suggest that Pt–Se nanozymes effectively suppress the early progression of OA with an Osteoarthritis Research International Association score reduction of 68.21% and 82.66% for 4 and 8 weeks, respectively. In conclusion, this study provides a promising strategy to regulate inflammatory responses by macrophage repolarization processes for OA therapeutic.

研究领域: 纳米技术 · 生物医学工程 · 药理学 · 免疫学 · 骨科
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ACS Nano · 2023 · IF 17.1

Nanoparticles Hitchhike on Monocytes for Glioblastoma Treatment after Low-Dose Radiotherapy

Jing Kuang,Zhi-Yong Rao,Di-Wei Zheng,Dong Kuang,Qian-Xiao Huang,Ting Pan,Hao Li,Xuan Zeng,Xian-Zheng Zhang

Glioblastomas (GBMs) are aggressive primary brain tumors with fatal outcome. Traditional chemo-radiotherapy has poor therapeutic effect and significant side effects, due to the drug and radiotherapy (RT) resistance, natural blood-brain barrier, and high-dose RT damage. Even more, tumor-associated monocytes (macrophages and microglia, TAMs) constitute up to 30%–50% of the GBM cellular content, and the tumor microenvironment (TME) in GBM is extremely immunosuppressive. Here, we synthesized nanoparticles (D@MLL) that hitchhike on circulating monocytes to target intracranial GBMs with the assistance of low-dose RT. The chemical construction of D@MLL was DOX·HCl loaded MMP-2 peptide-liposome, which could target monocytes by the surface modified lipoteichoic acid. First, low-dose RT at the tumor site increases monocyte chemotaxis and induces M1 type polarization of TAMs. Subsequently, the intravenous injected D@MLL targets circulating monocytes and hitchhikes with them to the central site of the GBM area. DOX·HCl was then released by the MMP-2 response, inducing immunogenic cell death, releasing calreticulin and high-mobility group box 1. This further contributed to TAMs M1-type polarization, dendritic cell maturation, and T cell activation. This study demonstrates the therapeutic advantages of D@MLL delivered by endogenous monocytes to GBM sites after low-dose RT, and it provides a high-precision treatment for GBMs.

CAS / MDL: 8002-43-5 12031-82-2
研究领域: 肿瘤学 · 神经科学 · 药学 · 放射肿瘤学 · 免疫学
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2023 · IF 5.8

Photoresponsive metal-organic framework with combined photodynamic therapy and hypoxia-activated chemotherapy for the targeted treatment of rheumatoid arthritis

Shixin Zhang,Miaomiao Zhang,Jingbo Zhang,Ge Li,Xinyue Lu,Fengying Sun,Wenhua Liu

Activated M1-type macrophages, which produce inflammatory factors that exacerbate rheumatoid arthritis (RA), represent crucial target cells for inhibiting the disease process. In this study, we developed a novel photoresponsive targeted drug delivery system (TPNPs-HA) that can effectively deliver the hypoxia-activated prodrug tirapazamine (TPZ) specifically to activated macrophages. After administration, this metal-organic framework, PCN-224, constructed uing the photosensitizer porphyrin, exhibits the ability to generate excessive toxic reactive oxygen species (ROS) when exposed to near-infrared light. Additionally, the oxygen-consumed hypoxic environment further activates the chemotherapeutic effect of TPZ, thus creating a synergistic combination of photodynamic therapy (PDT) and hypoxia-activated chemotherapy (HaCT) to promote the elimination of activated M1-type macrophages. The results highlight the significantly potential of this photoresponsive nano-delivery system in providing substantial relief for RA. Furthermore, these findings support its effectiveness in inhibiting the disease process of RA, thereby offering new possibilities for the development of precise and accurate strategies for RA.

CAS / MDL: 5471-63-6
研究领域: 药学 · 生物医学工程 · 免疫学 · 风湿病学
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Materials Science & Engineering C-Materials for Biological Applications · 2020 · IF 5.88

κ/β-Carrageenan oligosaccharides promoting polarization of LPS-activated macrophage and their potential in diabetes wound healing

Rijian Song,Xuan Mao,Shunqing Tang

Here we prepared a low-degree-sulfated κ/β-carrageenan oligosaccharide (L-DS-KOS) by DMSO-methanol desulfation method, and fabricated a sponge dressing for the wound healing of diabetic rats. The immunomodulatory effects of L-DS-KOS on M1-like macrophages were evaluated. Results showed that L-DS-KOS could effectively promote the secretion of anti-inflammatory factors and accelerate polarization of LPS-activated macrophages from M1 to M2 type. The gross examination result showed that the sponge dressing with the mass ratio of L-DS-KOS: collagen = 3: 7 could effectively accelerate the repair process of the full-thickness excisional wound in diabetic rats; and H&E and Masson staining results disclosed that the L-DS-KOS/collagen dressing could better shorten the inflammation period of the wound site, and improve the process of collagen deposition and epithelial formation, thereby promote the repair of skin wounds in diabetic rats. These results demonstrate that L-DS-KOS has potential to be used as a new type of immunomodulatory biomaterial for diabetic wound dressings.

研究领域: 免疫学 · 药剂学 · 伤口愈合 · 生物材料
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NPG Asia Materials · 2022 ·Vol. 14 ·期 1 ·1-11 · IF 10.761

NSC-derived extracellular matrix-modified GelMA hydrogel fibrous scaffolds for spinal cord injury repair

Chen Zheng,Wang Lin,Chen Chichi,Sun Jie,Luo Junchao,Cui Wenguo,Zhu Can,Zhou Xiaozhong,Liu Xingzhi,Yang Huilin,Shi Qin

Cell-derived extracellular matrix (ECM) has been applied in spinal cord injury (SCI) regeneration because of its various biological functions. However, insufficient mechanical properties limit its wide application. Herein, we developed GelMA/ECM hydrogel fibrous scaffolds (GelMA/ECM scaffolds) that can recruit and enhance the differentiation of neural stem cells (NSCs) by electrospinning and decellularization techniques. Moreover, the GelMA/ECM scaffolds had good mechanical properties and reinforced cell adhesion and proliferation. Compared to GelMA hydrogel fibrous scaffolds (GelMA scaffolds), GelMA/ECM scaffolds promoted more NSCs toward neurons by markedly enhancing the expression of MAP-2 and Tuj-1 and decreasing GFAP expression. In addition, the GelMA/ECM scaffolds significantly reduced the proportion of M1-phenotype macrophages, which is favorable for SCI repair. In vivo, the GelMA/ECM scaffolds recruited NSCs at the injured site, promoted neuron regeneration, and reduced the formation of glial scars and the inflammatory response, which further led to a significant improvement in the functional recovery of SCI. Therefore, this scaffold shows potential in regenerative medicine, mainly in SCI.

CAS / MDL: 111-30-8 920-66-1
研究领域: 再生医学 · 生物医学工程 · 神经科学 · 组织工程
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