Advanced Healthcare Materials
·
2022
·Vol. 11
·期 19
·2200776
·
IF 11.092
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
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免疫学
·
纳米医学
✓ 已验证
DOI
PubMed
高影响因子
Reproductive Sciences
·
2025
·
IF 2.5
Qiu Yingying,Wei Xinjun,Cao Jian,Wang Jindan,Dou Qianru,Zhou Fangfang,Chen Xi,Liu Yongli,Wan Guiping,Huang Meihua,Li Zhenli,Gui Tao
Adenomyosis (AM), a gynecological disorder that severely affects female reproductive health. AM-associated macrophage (AAM) polarization-induced epithelial–mesenchymal transition (EMT) is a key driver of AM progression. In this study, we investigated the role and underlying mechanisms of endometrial mesenchymal stem cell (eMSC)-derived exosomes in regulating AAM polarization and the subsequent EMT of endometrial epithelial cells (EECs). In vitro coculture studies revealed that AM eutopic eMSCs markedly induced M2 macrophage polarization via exosomes and promoted EMT of EECs. Differentially expressed microRNAs (DE-miRNAs) between exosomes derived from normal eMSCs (N-eMSCs) and AM eutopic eMSCs (A-eMSCs) were identified using miRNA sequencing and miR-4669 was found to be the most significantly upregulated miRNA. Internalization of exosomal miR-4669 by macrophages induced their polarization toward the M2 phenotype and promoted the EMT of EECs. Mechanistic analysis using luciferase assay, mRNA sequencing, and rescue experiments revealed that miR-4669 induced M2 macrophage polarization via downregulation of DUSP6 and activation of MAPK/ERK signaling. The polarized M2 macrophages promoted the EMT of ISK cells via TGF-β1 secretion. In an AM xenograft mouse model, miR-4669 depletion inhibited AM progression by targeting the DUSP6/ERK1/2 pathway in macrophages. Overall, AM A-eMSC-derived exosomal miR-4669 facilitates M2 macrophage polarization by targeting the DUSP6/ERK signaling pathway, thereby promoting EMT of EECs via TGF-β1 secretion. These findings open avenues for developing novel preventive and therapeutic strategies for AM. Graphical
研究领域:
妇科学
·
干细胞生物学
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分子生物学
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细胞信号传导
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癌症生物学
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免疫学
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microRNA研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2025
·
IF 5.6
Ke Wang,Xiaomin Xia,Nan Wang,Jie Liu,Xue Li
Macrophage extracellular traps (METs) are protein network structures released by macrophages during immune defense initiation and inflammation regulation. Evidence shows that these protein structures can help kill pathogens. However, overproduction of METs can harm organisms. Therefore, novel strategies to inhibit the excessive production of METs during immune reactions need to be developed. This study introduces a novel type of anti-inflammatory and antibacterial nanocomposites (i.e., ZIF-8/Ce@rutin NPs) developed by doping the nanozyme Ce into the antibacterial zeolitic imidazole framework-8 (ZIF-8) and then loading the reactive oxygen species (ROS) scavenger rutin via electrostatic adsorption. Results showed that ZIF-8/Ce@rutin exerted bactericidal effects on gram-positive and -negative bacteria, thereby inhibiting MET production from the source. Furthermore, ZIF-8/Ce@rutin scavenged ROS and induced macrophage polarization into the anti-inflammatory M2 type, thereby inhibiting MET progression. This research shows that ZIF-8/Ce@rutin can restrain MET overproduction, providing a theoretical basis for using ZIF-8/Ce@rutin to treat inflammatory and infectious diseases.
研究领域:
纳米技术
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免疫学
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炎症研究
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生物医学工程
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2020
·
IF 0
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.
研究领域:
生物医学工程
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纳米技术
·
癌症治疗
·
材料科学
✓ 已验证
产品关联
DOI
Biomaterials Advances
·
2025
·
IF 6
Shuting Peng,Lantao Wang,Zhengfeng Lu,Xinyi Yang,Yanxin Lu,Zhengxiao Wang,Qingxin Wu,Xiaofei Qin
The hypoxic, hyperglycemic, ischemic and inflammatory at the chronic diabetic wound microenvironment often leads to persistent oxidative stress and dysfunctional immune responses, as evidenced by hindrance of angiogenesis, neuropathy and impaired macrophage M2-type transition. In addition, bacterial infections lead to further exacerbation of chronic inflammatory responses, which severely impedes wound healing. In this study, hydroxypropyl chitosan (HCS) and 2,3,4-trihydroxybenzaldehyde (TBA) hydrogel was prepared via a one-step method, while Fe 3+ was used to initiate the in-situ oxidative polymerization of pyrrole (Py) in the hydrogel network, that conferred the HCS-TBA@Py hydrogel with excellent electrical conductivity. The outstanding physicochemical properties of the hydrogel, including swelling ability, injectability and electrosensitivity, confirmed its potential for applications in rapid filling of irregular wounds and strain sensors. Meanwhile, HCS-TBA@Py hydrogel can effectively scavenge reactive oxygen species and inhibit bacterial growth. More importantly, the combination of HCS-TBA@Py with electrical stimulation (ES) can effectively enhance the proliferation and migration of endothelial cells, promote axonal growth of nerve cells, rapid angiogenesis and accomplish the phagocytosis of M1 macrophages while realizing the M2 polarization of macrophages, comprehensively and systematically ameliorating the healing of diabetic wounds. This advanced study opens a meaningful way for chronic diabetic wound repair.
研究领域:
生物材料
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组织工程
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伤口愈合
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糖尿病治疗
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纳米医学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2023
·Vol. 11
·期 9
·3227-3240
·
IF 6.6
Xiaohui Cai,Yutong He,Liu Cai,Jiamian Zhan,Qian Li,Saiqiong Zhong,Honghao Hou,Wenya Wang,Xiaozhong Qiu
Injectable self-healing hydrogel dressings with excellent elasticity and multifunctional repair effects have been in high demand in wound healing applications, while maintaining stable elasticity in injectable multifunctional hydrogel dressings is still a challenge. Based on carboxymethyl chitosan (CMCS), curcumin–gelatin nanoparticles (CG NPs), and sodium alginate oxide (OSA), we developed a double-crosslinking injectable elastic self-healing hydrogel without any chemical cross-linking agent as a multifunctional wound healing dressing. CG NPs were more stable than pure curcumin (Cur) nanoparticles and could regulate the cross-linking of injectable hydrogels for high elasticity and rapid self-healing. We found that the CG NPs endowed the injectable hydrogel with good anti-inflammatory, antibacterial, and reactive oxygen scavenging activities and could significantly shorten the wound healing time in infected full-thickness skin defect rats by promoting the polarization of M2-type macrophages, reducing oxidative damage, accelerating collagen deposition, enhancing granulation formation, and elevating angiogenesis. Taken together, the tunable elastic injectable hydrogel dressing exhibited a long-term service life with sustained repair function and can be taken as an optimal candidate for bacteria-infected wound healing.
研究领域:
生物材料
·
伤口愈合
·
纳米技术
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Science & Engineering C-Materials for Biological Applications
·
2020
·
IF 5.88
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
✓ 已验证
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
·
IF 10
Ziyang Sun,Ruochuan Huang,Hao Lyu,Xin Yu,Wenzhao Wang,Jinghang Li,Xingyu Lu,Chengchen Guo
Silk fibroin derived from the domesticated silkworm Bombyx mori is a protein-based biopolymer with low immunogenicity, intrinsic biodegradability, and tunable mechanical properties, showing great potential in biomedical applications. Using chemical modification to alter the primary structure of silk fibroin enables the expanded generation of new silk-based biomaterials. Inspired by the molecular structure of hyaluronic acid, which is enriched in carboxyl groups, an efficient method with scaling-up potential to achieve controlled carboxylation of silk fibroin to prepare silk acid (SA) is reported, and the biological properties of SA are further studied. The SA materials show tunable hydrophilicity and enzymatic degradation properties at different carboxylation degrees (CDs). Subcutaneous implantation in mice for up to 1 month reveals that the SA materials with a high CD present enhanced degradation while causing a mild foreign-body response, including a low inflammatory response and reduced fibrotic encapsulation. Immunofluorescence analysis further indicates that the SA materials show pro-angiogenesis properties and promote M2-type macrophage polarization to facilitate tissue regeneration. This implies great promise for SA materials as a new implantable biomaterial for tissue regeneration.
研究领域:
生物医学工程
·
材料科学
·
组织工程
·
生物材料
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Translational Medicine
·
2025
·Vol. 23
·期 1
·1-19
·
IF 7.5
Xing Chunyang,Hu Wei,Zhao Liyuan
Background Osteosarcoma (OS) is one of the most common malignancies arising in bone. Hypoxia and immune regulation are pivotal in tumor biology. However, their combined effects and mechanisms in OS remain understudied. This study aimed to explore the role and mechanism of hypoxic-induced M2 macrophages in promoting the progression of OS.Methods Differentially expressed proteins in hypoxic macrophage supernatants were detected by antibody array. Cell functional experiments, siRNA-mediated gene silencing, and overexpression transfection were used to study osteopontin (OPN) and its supernatant effect. Bioinformatics analysis was applied to investigate downstream targets and pathways, and a xenograft model was established to assess in vivo effects.Results Our data revealed that hypoxic M2 macrophage supernatant enhanced OS malignancy and epithelial-mesenchymal transition, activating cancer pathways. Hypoxia upregulated OPN in M2 macrophages, and OPN inhibition reduced its tumor-promoting effect. Early growth response 3 (EGR3) was differentially expressed in OS cells treated with the supernatant, and its overexpression inhibited OS cell migration, reversing tumor promotion. Interferon-stimulated gene 15 (ISG15), a key differentially expressed gene related to OPN and EGR3 overexpression, inhibited OS cell proliferation and migration. Additionally, OPN increased retinoic acid-inducible gene I (RIG-I) expression and enhanced signal transducer and activator of transcription 3, nuclear factor kappa B, and extracellular signal-regulated kinase signaling, while EGR3 and ISG15 overexpression inhibited these effects. Silencing ISG15 restored pathway activation and reversed the inhibitory effect of EGR3 on OS cell migration. Dual-Luciferase reporter gene assay confirmed that EGR3 activates ISG15 transcription. OPN treatment upregulated DNA (cytosine-5)-methyltransferase 1 (DNMT1) expression, and ChIP assays demonstrated that EGR3 overexpression enhanced DNMT1 binding to the EGR3 promoter. These findings suggest that OPN promotes OS malignancy by downregulating EGR3 and ISG15, and by enhancing RIG-I expression, as validated in a xenograft model of OS.Conclusion Our findings demonstrate that hypoxic-induced M2 macrophages promote OS progression through OPN-dependent mechanisms, including inhibition of EGR3 and ISG15 expression and upregulation of RIG-I.Graphical abstract
研究领域:
癌症生物学
·
免疫学
·
分子生物学
·
细胞生物学
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肿瘤微环境
·
信号转导
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
·Vol. 12
·期 12
·2201548
·
IF 10
Yanyan Zhou,Zihe Hu,Wenjing Jin,Haiyan Wu,Minghao Zuo,Changyu Shao,Yanhua Lan,Yang Shi,Ruikang Tang,Zhuo Chen,Zhijian Xie,Jue Shi
Inspired by the bionic mineralization theory, organic–inorganic composites with hydroxyapatite nanorods orderly arranged along collagen fibrils have attracted extensive attention. Planted with an ideal bone scaffold will contribute greatly to the osteogenic microenvironment; however, it remains challenging to develop a biomimetic scaffold with the ability to promote intrafibrillar mineralization and simultaneous regulation of immune microenvironment in situ. To overcome these challenges, a scaffold containing ultra-small particle size calcium phosphate nanocluster (UsCCP) is prepared, which can enhance bone regeneration through the synergetic effect of intrafibrillar mineralization and immunomodulatory. By efficient infiltration into collagen fibrils, the UsCCP released from the scaffold achieves intrafibrillar mineralization. It also promotes the M2-type polarization of macrophages, leading to an immune microenvironment with both osteogenic and angiogenic potential. The results confirm that the UsCCP scaffold has both intrafibrillar mineralization and immunomodulatory effects, making it a promising candidate for bone regeneration.
研究领域:
生物材料
·
组织工程
·
生物医学工程
·
材料科学
·
免疫学
·
再生医学
✓ 已验证
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2020
·
IF 7.242
Ying-Zheng Zhao,Zhi-Wei Huang,Yuan-Yuan Zhai,Yannan Shi,Chu-Chu Du,Jiaoyuan Zhai,He-Lin Xu,Jian Xiao,Longfa Kou,Qing Yao
Macrophage polarization is one of the main factors contributing to the proinflammatory milieu of transplanted islets. It causes significant islet loss. Bilirubin exhibits protective effects during the islet transplantation process, but the mode of delivering drugs along with the islet graft has not yet been developed. In addition, it remains unclear whether bilirubin or its derivatives can modulate macrophage polarization during islet transplantation. Therefore, this study aimed to develop an ε-polylysine-bilirubin conjugate (PLL-BR) to encapsulate the islets for protection and to explore its macrophage modulation activities. In in vitro studies, the PLL-BR was shown to tightly adhere to the islet surface. It also exhibited enhanced cytoprotective effects against oxidative and inflammatory conditions by promoting M2-type macrophage polarization. In i n vivo studies, the PLL-BR-protected islets successfully prolonged the euglycemia period in diabetic mice and accelerated the blood glucose clearance rate by maintaining the insulin secretion function. Compared to the untreated islets, the PLL-BR-encapsulated islets induced anti-inflammatory responses that were characterized by elevated levels of M2 macrophage markers and local vascularization . In conclusion, PLL-BR can be used as a tool for reprograming macrophage polarization while providing a more efficient immune protection for transplanted islets. Statement of significance Macrophage polarization is one main factor that caused significant loss of transplanted islets. Bilirubin possesses protective effects toward pancreatic islet, but how to deliver the drug along with the islet graft has not yet been harnessed. More importantly, whether bilirubin or its derivatives could modulate macrophage polarization during the host rejections has also not been answered. In this study, we developed an ε-polylysine-bilirubin conjugate (PLL-BR) to encapsulate the islets and explore its role in macrophage modulation activities. PLL-BR could attach to the surface of islets and exerted high oxidation resistance and anti-inflammatory effect. For the first time, we demonstrate that bilirubin and its derivatives effectively promoted the M2-type macrophage polarization, and optimize the immune microenvironment for islets survival and function.
研究领域:
移植免疫学
·
药学
·
糖尿病研究
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免疫学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Small
·
2023
·Vol. 19
·期 19
·2205904
·
IF 13.3
Yanlin Deng,Yatian Fu,Song Lin Chua,Bee Luan Khoo
Components of the tumor microenvironment (TME), such as tumor-associated macrophages (TAMs), influence tumor progression. The specific polarization and phenotypic transition of TAMs in the tumor microenvironment lead to two-pronged impacts that can promote or hinder cancer development and treatment. Here, a novel microfluidic multi-faceted bladder tumor model (TAM PIEB ) is developed incorporating TAMs and cancer cells to evaluate the impact of bacterial distribution on immunomodulation within the tumor microenvironment in vivo. It is demonstrated for the first time that biofilm-induced inflammatory conditions within tumors promote the transition of macrophages from a pro-inflammatory M1-like to an anti-inflammatory/pro-tumor M2-like state. Consequently, multiple roles and mechanisms by which biofilms promote cancer by inducing pro-tumor phenotypic switch of TAMs are identified, including cancer hallmarks such as reducing susceptibility to apoptosis, enhancing cell viability, and promoting epithelial-mesenchymal transition and metastasis. Furthermore, biofilms formed by extratumoral bacteria can shield tumors from immune attack by TAMs, which can be visualized through various imaging assays in situ. The study sheds light on the underlying mechanism of biofilm-mediated inflammation on tumor progression and provides new insights into combined anti-biofilm therapy and immunotherapy strategies in clinical trials.
研究领域:
癌症生物学
·
免疫学
·
微生物学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）