BIOMATERIALS
·
2024
·
IF 12.8
Fuhong Yang,Jingqi Lv,Yanli Huang,Wen Ma,Zhen Yang
As regulators and promotors of joint erosion, pro-inflammatory M1-like macrophages play pivotal roles in the pathogenesis of rheumatoid arthritis (RA). Here, we develop a supramolecular self-assembly (PCSN@MTX) of molybdenum (Mo) based polyoxometalate (POM), β-cyclodextrin (β-CD), and methotrexate (MTX), in which the MTX is loaded by host-guest interaction. PCSN@MTX shows inhibition of synovial M1-like macrophages polarization to alleviate RA. PCSN@MTX has demonstrated ultrasound (US) augmented catalytic behavior in consuming ROS and generating oxygen (O 2 ) with accelerated conversion of Mo 5+ to Mo 6+ in the POM. In the collagen-induced arthritis mouse model, after systemical administration, the pH-responsive PCSN@MTX shows enhanced accumulation in the acidic joints by in-situ self-assembly. The host-guest complexation between MTX and β-CD is broken via US, achieving an on-demand burst release of MTX. The released MTX and ROS-scavenging synergistically facilitate the M1-to-M2 macrophage phenotype switching, which effectively alleviates RA disease progress under US irradiation. This study provides a paradigm for RA therapy with a promising US-augmented strategy.
研究领域:
药理学
·
风湿病学
·
纳米医学
·
炎症研究
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Meng Zhu,Jinzhao Ou,Yuzhou Chen,Ye Tian,Wei Song,Xiaohua Hu,Xiaoyan Ju,Shidong Jiang,Sha Huang,Zhongwei Niu
Macrophage polarization and phenotypic switching have a significant impact on the immune microenvironment of wounds, making them crucial for wound healing. Creating immune-adapted microenvironment throughout the wound repair process by regulating macrophage polarization supports rapid wound healing. We explored the segmented use of M1-polarizing and M2-polarizing materials at different healing stages and found that this combination can significantly shorten the healing time. The macrophage polarization could be adjusted to M1 phenotype and M2 phenotype by selective modification of chitosan with dicyandiamide or polyethylene glycol, respectively. In a rat full-thickness infected wound model, combining dicyandiamide modified chitosan (DICY-CS) for M1 macrophage polarization in the inflammatory phase and PEGylated chitosan (PEG-CS) for M2 macrophage polarization in the proliferative phase significantly reduced wound healing time. A higher degree of re-epithelialization, collagen deposition and neovascularization were observed in wounds treated with this combination approach compared to the antimicrobial agents Silvadene and DICY-CS or PEG-CS alone. The use of different macrophage polarizing materials separately in different healing stages provided an optimal immune microenvironment and accelerated wound healing. This strategy provides a more comprehensive understanding of the wound healing process. It will be a new insight for the treatment of more complex and difficult-to-heal wounds such as pressure ulcers and diabetic wounds.
研究领域:
免疫学
·
生物医学工程
·
伤口愈合
·
组织工程
✓ 已验证
DOI
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Xiaoyou Zhang,Zichen Yang,Hui Zhi,Shiyu Chen,Weimin Yin,Lulu An,Rongjie Li,Yanni Cai,Caoyi You,Haiqing Dong,Yongyong Li,Yan Li
Tumor-associated macrophages (TAMs) play a crucial role in tumor progression and therapy resistance. The mechanochemical synergy has emerged as a key mechanism regulating the polarization of TAMs toward the tumor-promoting M2 phenotype. However, whether this synergy can be exploited to reprogram TAMs to a tumor-suppressive M1 phenotype remains an unexplored therapeutic strategy. Here, we report a mechanochemically synergistic nanoplatform, RMSN@EXO, designed to reprogram TAMs efficiently and enhance the anti-tumor immune microenvironment. This nanoplatform is composed of mesoporous silica nanoparticles (MSNs) with tailored elasticity and is loaded with the immunomodulator resiquimod (R848). Both MSNs and R848 were identified through screening based on the M1-specific metabolic marker, lactate. And RMSN is subsequently encapsulated within exosomes derived from M1 macrophage. Surprisingly, this nanoplatform efficiently reprograms TAMs into a pro-inflammatory M1-phenotype more effectively than either R848 or MSNs alone. Benefiting from the superior penetration of mechanically tailored MSNs in the TME and the exosome-mediated tumor targeting, RMSN@EXO exhibits enhanced accumulation in hypoxic regions of solid tumors. In vivo experiments further show that repolarized TAMs in hypoxic areas have a significant inhibitory effect on tumor growth. In conclusion, this study establishes a “nano-mechanochemical synergy” strategy to efficiently reprogram TAMs to enhance robust anti-tumor immunity. It provides a fundamental framework for designing nanomedicines based on mechanical properties to improve cancer immunotherapy.
研究领域:
纳米医学
·
免疫治疗
·
癌症生物学
·
生物工程
·
材料科学
·
生物力学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Qiao Zhang,Chaoqian Lou,Hang Li,Yanyan Li,Hongjie Zhang,Zimeng Li,Ganggang Qi,Xia Cai,Qiaojie Luo,Lijie Fan,Xiaojun Li,Weiwei Lao,Weipu Zhu,Xiaodong Li
Barrier membranes play a pivotal role in the success of guided periodontal tissue regeneration. The biodegradable barriers predominantly used in clinical practice often lack sufficient barrier strength, antibacterial properties, and bioactivity, frequently leading to suboptimal regeneration outcomes. Although with advantages in mechanical strength, biodegradability and plasticity, bioinert aliphatic polyesters as barrier materials are usually polymerized via toxic catalysts, hard to be functionalized and lack of antibacterial properties. To address these challenges, we propose a new concept that controlled release of bioactive substance on the whole degradation course can give a bioinert aliphatic polyester bioactivity. Thus, a Zn-based catalytic system for polycondensation of dicarboxylic acids and diols is created to prepare zinc covalent hybrid polyester (PBS/ZnO). The atomically-dispersed Zn 2+ ions entering main chain of polyester molecules endow PBS/ZnO barrier with antibacterial properties, barrier strength, excellent biocompatibility and histocompatibility. Further studies reveal that relying on long-term controlled release of Zn 2+ ions, the PBS/ZnO membrane greatly expedites osteogenetic effect in guided tissue regeneration (GTR) by enhancing the mitochondrial function of macrophages to induce M2 polarization. These findings show a novel preparation strategy of bioactive polyester biomaterials based on long term controlled release of bioactive substance that integrates catalysis, material structures and function customization.
研究领域:
材料科学
·
生物材料
·
组织工程
·
牙科科学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Liya Feng,Yuanxin Wang,Xiangyue Wang,Baochan Li,Yifan Liu,Wanying Zhang,Jianbo Ji,Lijun Shao,Xiuli Guo
In the tumor microenvironment (TME), tumor associated macrophages (TAMs) often exhibit a preference for M2-like phenotype, which supports tumor progression under hypoxia. The underlying mechanisms driving the behavior of hypoxic TAMs are highly complex. Recently, exosomal long non-coding RNAs (lncRNAs) derived from non-cancerous cells within TME have attracted more attention from researchers. In the present study, we investigated the function of exosomal lncRNA MIR210HG derived from hypoxic TAMs in triple negative breast cancer (TNBC). Results showed that MIR210HG was significantly upregulated in hypoxic TAMs, their exosomes, and exosomes-treated TNBC cells. When MIR210HG was suppressed, the expression of M2-polarization markers and proteins associated with the PI3K/Akt/mTOR pathway in hypoxic TAMs was notably inhibited. Moreover, the suppression of TAM-derived exosomal MIR210HG effectively inhibited the migration, invasion and vasculogenic mimicry (VM) formation of TNBC cells. Notably, dual inhibition of both exosomal and endogenous MIR210HG in tumor cells synergistically restricted TNBC metastasis of in vivo . Mechanistically, we elucidated that MIR210HG promoted the malignant phenotypes of TNBC by upregulating the expression of HIF-1α protein, which in turn initiated RASSF7 transcription, resulting in the promotion of epithelial-mesenchymal transition (EMT) process. Collectively, our results identified MIR210HG as a key molecule mediating exosome-based communication from hypoxic TAMs to TNBC cells and revealed its pro-metastatic role, Consequently, MIR210HG emerges as a highly promising therapeutic target of TNBC.
研究领域:
癌症生物学
·
分子生物学
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免疫学
·
细胞生物学
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遗传学
·
生物信息学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2023
·Vol. 21
·期 1
·1-14
·
IF 10.2
Ren Yiming,Chen Yi,Chen Wei,Deng Haotian,Li Peiqi,Liu Yubo,Gao Cangjian,Tian Guangzhao,Ning Chao,Yuan Zhiguo,Sui Xiang,Liu Shuyun,Guo Quanyi
Successful biomaterial implantation requires appropriate immune responses. Macrophages are key mediators involved in this process. Currently, exploitation of the intrinsic properties of biomaterials to modulate macrophages and immune responses is appealing. In this study, we prepared hydrophilic nanofibers with an aligned topography by incorporating polyethylene glycol and polycaprolactone using axial electrospinning. We investigated the effect of the nanofibers on macrophage behavior and the underlying mechanisms. With the increase of hydrophilicity of aligned nanofibers, the inflammatory gene expression of macrophages adhering to them was downregulated, and M2 polarization was induced. We further presented clear evidence that the inflammasome NOD-like receptor thermal protein domain associated protein 3 (NLRP3) was the cellular sensor by which macrophages sense the biomaterials, and it acted as a regulator of the macrophage-mediated response to foreign bodies and implant integration. In vivo, we showed that the fibers shaped the implant-related immune microenvironment and ameliorated peritendinous adhesions. In conclusion, our study demonstrated that hydrophilic aligned nanofibers exhibited better biocompatibility and immunological properties.
研究领域:
生物材料科学
·
免疫学
·
组织工程
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 16.744
Rajiu Venkatesan,Hao Xiong,Yuejun Yao,Jayachandra Reddy Nakkala,Tong Zhou,Shifen Li,Cunyi Fan,Changyou Gao
The chronic autoimmune of rheumatoid arthritis (RA) usually results in inflammation of synovial joint, leading to pain, and destruction of cartilage and bone. Activated macrophages (M1 macrophages) actively take part in the RA pathogenesis, intensifying the inflammation and destruction of bone and cartilage. In this study, a nanoplatform was developed by grafting PEGylated folate acid (FA) and conjugating IL-4 onto gold nanocages (AuNCs), into the nanopores of which anti-inflammatory drug methylprednisolone (MP) was loaded. The [email protected] conjugates (consisting of PEGylated FA, IL-4 and MP) effectively targeted the folate receptors overexpressed on M1 macrophage surface, down-regulating the expression of M1 marker and up-regulating the M2 markers. The expression of pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β was significantly suppressed by the MP-AuNCs and [email protected] both in vitro and in vivo . The AuNCs conjugates could act as a contrast agent for photoacoustic (PA) phantom and CT imaging. The therapeutic efficacy of different AuNCs conjugates on RA in a model of rat adjuvant-induced arthritis (AIA) was verified by ELISA, histological, and Western blot analyses, revealing the therapeutic potential through immune-modulatory function on macrophages with [email protected] being the best and followed by MP-AuNCs.
研究领域:
纳米技术
·
免疫学
·
药学
·
医学成像
✓ 已验证
DOI
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2021
·Vol. 31
·期 43
·2105348
·
IF 18.808
Yanhuizhi Feng,Huai-Ling Gao,Di Wu,Yu-Teng Weng,Ze-Yu Wang,Shu-Hong Yu,Zuolin Wang
Mucogingival surgery has become a common procedure for soft gingival tissue reparation in dental clinical practice, which mainly relies on autograft or commercial collagen membranes (CM). However, the autograft faces grand challenges in source availability and long-term post-surgery pain management, and the CM is restricted by its poor mechanical properties in an aqueous environment. Here, it is reported that a bio-inspired lamellar chitosan scaffold (LCS) with long range ordered porous structure, manufactured through a bidirectional freezing method, can serve as a promising gingival tissue engineering material. The LCS not only exhibits excellent mechanical properties in the hydrated state but also accelerates vessel formation and soft tissue regeneration in vivo. Most interestingly, the LCS is found to be capable of inducing macrophage differentiation to M2 macrophages, which is thought to play an important role in tissue regeneration. These advantages combined with its easy and low-cost preparation process make the LCS a promising candidate for dental clinical applications.
研究领域:
口腔临床实践
·
组织工程
·
生物医用材料
✓ 已验证
DOI
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
Nanophotonics
·
2021
·Vol. 10
·期 12
·3267-3278
·
IF 8.449
Shanshan Liu,Jiawen He,Ruixiang Song,Mengmeng Zhang,Lianghao Huang,Jing Chen,Meng Wang,Fang Liu,Feifan Zhou
Treatment of pancreatic cancer is faced with great difficulties and challenges due to high lethality and metastasis. Synergism of targeted therapy and immunotherapy has been considered as ideal strategy to both eliminate primary tumors and control metastases. For the treatment of advanced pancreatic cancer, we demonstrated a local photothermal therapy (PTT) following administration of monoclonal antibody of programmed death ligand 1 (αPD-L1). Fe 2 P nanorods were employed as a Fenton agent and photothermal agent, which modified with DSPE-PEG 2000 -Mal for improved biocompatibility and Mal mediated-antigen presentation. Under a low dose laser irradiation at 980 nm, Fe 2 P-PEG-Mal nanorods (NRs) mediated PTT could induce immunogenic tumor cell death that can cause dendritic cells (DCs) infiltration and maturation. In a bilateral pancreatic tumor model, the local treatment of NRs-PTT on primary tumor could cause the increased infiltration of cytotoxic T lymphocytes (CTLs) and decreased residential of M2 macrophages in untreated distal tumors. Furthermore, subsequently intervened αPD-L1 could enhance cell death triggered by CTLs in distal tumors through reversing immunosuppression. An orthotopic pancreatic tumor model was used to further confirm the therapeutic outcome. Finally, the combination of NRs based PTT and αPD-L1 based immunotherapy was able to significantly eliminate orthotopic pancreatic tumors and reduce mesentery metastases. Thus, the strategy may provide a more effective treatment for pancreatic cancer.
研究领域:
肿瘤学
·
纳米技术
·
免疫疗法
·
生物医学工程
✓ 已验证
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Jiale Jin,Yiqi Yang,Jian Yang,Zeyu Sun,Dongyu Wang,Yifang Qin,Chengxin Ruan,Dongdong Li,Yi Pan,Jiangdong Wu,Chi Zhang,Yihe Hu,Pengfei Lei
Diabetic infected bone defects (DIBD) with abnormal immune metabolism are cline to the hard-to-treat bacterial infections and delayed bone regeneration, which present significant challenges in clinic. Control of immune metabolism is believed to be important in regulating fundamental immunological processes. Here, we developed a macrophage metabolic reprogramming hydrogel composed of modified silk fibroin (Silk-6) and poly- l -lysine (ε-PL) and further integrated with M2 Macrophage-derived Exo (M2-Exo), named as Silk-6/ε-PL@Exo. This degradable hydrogel showed a broad-spectrum antibacterial performance towards both Gram-positive and -negative bacteria. More importantly, the release of M2-Exo from Silk-6/ε-PL@Exo could target M1 macrophages, modulating the activity of the key enzyme hexokinase II (HK2) to control the inflammation-related NF-κB pathway, alleviate lactate accumulation, and inhibit glycolysis to normalize the cycle, thereby promoting M1-to-M2 balance. Using a rat model of DIBD, Silk-6/ε-PL@Exo hydrogel promoted infection control, balanced immune responses and accelerated the bone defect healing. Overall, this study demonstrates that this Silk-6/ε-PL @Exo is a promising filler biomaterials with multi-function to treat DIBD and emphasizes the importance of metabolic reprogramming in bone regeneration.
研究领域:
生物材料
·
组织工程
·
免疫学
·
代谢生物学
·
骨科
✓ 已验证
DOI
PubMed
高影响因子
Biomaterials Advances
·
2025
·
IF 6
Long Yang,Yufei Liu,Yong Yang,Yuhu Zhou,Zihao Zou,Min He,Changlei Yang,Daizhu Yuan,Jieheng Wu,Chuan Ye
Artificial bone substitutes have garnered significant attention within the field of biomaterials, and the use of tissue engineering technology to repair bone defects has emerged as a promising alternative. However, when artificial bone substitutes are implanted in the body, they can induce many adverse cellular and tissue immune responses. In this study, we use coaxial electrospinning technology to fabricate microfiber with controllable diameter, excellent mechanical properties and surface porous structure. Poly(3-hydroxybutyrate- co -4-hydroxybutyrate) (P34HB) and polyethylene glycol (PEG) were used as shell solutions and polyvinyl alcohol (PVA) and bone morphogenetic protein-2 (BMP-2) peptides as core solutions. Compared to PVA/P34HB-PEG (P/P-P) scaffolds, PVA-BMP-2/P34HB-PEG (P-B/P-P) scaffolds polarized more human monocytic leukemia cell line (THP-1 cells) toward alternatively activated macrophages (M2), as demonstrated by increased M2 and decreased classically activated macrophage (M1) phenotypic marker expression in the cells. P-B/P-P microfibers have the potential to regulate the polarization state of macrophages, induce them to differentiate into an M2 phenotype and inhibit the inflammatory response of surrounding tissues. In addition, microfibers with a hollow porous structure facilitate the controlled release of BMP-2 peptides by regulating the fiber diameter, enhancing the differentiation of pre-osteoblastic cell line derived from mouse calvaria (MC3T3-E1) cells in an osteogenic direction and facilitating the repair of bone defects in vivo. This study presents microfibers essential for modulating the osteoimmune microenvironment, facilitating efficient bone regeneration.
研究领域:
生物材料
·
组织工程
·
免疫调节
·
骨再生
·
纳米纤维技术
·
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）