JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-26
·
IF 10.6
Qiu Shui,Cao Lili,Xiang Dingding,Wang Shu,Wang Di,Qian Yiyi,Li Xiaohua,Zhou Xiaoshu
To assess the efficacy of a novel 3D biomimetic hydrogel scaffold with immunomodulatory properties in promoting fracture healing. Immunomodulatory scaffolds were used in cell experiments, osteotomy mice treatment, and single-cell transcriptomic sequencing. In vitro, fluorescence tracing examined macrophage mitochondrial transfer and osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). Scaffold efficacy was assessed through alkaline phosphatase (ALP), Alizarin Red S (ARS) staining, and in vivo experiments. The scaffold demonstrated excellent biocompatibility and antioxidant-immune regulation. Single-cell sequencing revealed a shift in macrophage distribution towards the M2 phenotype. In vitro experiments showed that macrophage mitochondria promoted BMSCs’ osteogenic differentiation. In vivo experiments confirmed accelerated fracture healing. The GAD/Ag-pIO scaffold enhances osteogenic differentiation and fracture healing through immunomodulation and promotion of macrophage mitochondrial transfer.
研究领域:
生物材料
·
组织工程
·
再生医学
·
免疫学
·
干细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Zhuangzhuang Chu,Xingdan Liu,Tong Zhao,Dongya Jiang,Jing Zhao,Xiaohua Dong,Kelvin W.K. Yeung,Xuanyong Liu,Yun Liao,Liping Ouyang
Non-healing diabetic foot ulcers are the knotty public health issue due to the uncontrolled bacterial infection, prolonged inflammation, and inferior vessel remodeling. In this work, polypyrrole (Ppy) was added into the hybrid hydrogel containing polyvinyl alcohol (PVA), polyethylene glycol (PEG), and hyaluronan (HA) to acquire superior mechanism and photothermal ability. The Ppy composited hybrid hydrogel could effectively kill bacteria through accumulating heat on the hydrogel surface. RNA-Seq analysis shows that the heat accumulation could enhance phagosome of macrophage and M1 activation, which further accelerate bacteria clearance. Benefitting from the bacteria clearance, macrophage could transform its phenotype to M2 in Ppy composited hybrid hydrogel group with near infrared light (NIR) stimulation. The related genes expression in keratinization, keratinocyte differentiation, and establishment of the skin barrier in the skin were up-regulated and collagen and vascular endothelial growth factor (VEGF) expression level are also enhanced. In summary, Ppy composited hybrid hydrogel could effectively solve the issues of infection and poor wound healing in diabetic foot ulcers, making it an ideal candidate dressing for the treatment of chronic wounds.
研究领域:
生物医学工程
·
伤口愈合
·
组织工程
·
材料科学
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光热治疗
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感染控制
·
免疫学
✓ 已验证
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2025
·
IF 9.6
Yuanqi Chen,Kezheng Lei,Yinxi Li,Zhixiang Mu,Tengda Chu,Jiajun Hu,Bairui Zeng,Yi Wang,Jianliang Shen,Xiaojun Cai,Tianpeng Shi,Hui Deng
Oral mucosal wounds are more prone to inflammation due to direct exposure to various microorganisms. This can result in pain, delayed healing, and other complications, affecting patients' daily activities such as eating and speaking. Consequently, the overall quality of life for patients is significantly reduced. To address these challenges, we developed a multifunctional therapeutic nanoplatform, DATS@Arg-EA-SA, through the self-assembly of guanidinated dendritic peptides (Arg-EA-SA) that encapsulate diallyl trisulfide (DATS), a hydrogen sulfide (H 2 S) donor. The guanidine-rich surface of DATS@Arg-EA-SA efficiently neutralizes reactive oxygen species (ROS) in the ulcer microenvironment, generating nitric oxide (NO), which acts as the primary antimicrobial agent by disrupting bacterial membranes. Concurrently, the presence of glutathione triggers the release of H 2 S from DATS, providing supplementary antibacterial support. DATS@Arg-EA-SA effectively kills all bacteria, achieving results comparable to those of penicillin, a classical antibiotic. Moreover, it demonstrates superior sterilization efficacy against drug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), significantly outperforming penicillin. Following the initial antimicrobial phase, the nanoplatform transitions into an anti-inflammatory stage. H 2 S, in synergy with NO, facilitates the conversion of M1 macrophages to M2 macrophages, thereby reducing the expression of inflammatory factors. Importantly, the combination of H 2 S and NO provides effective analgesia by downregulating the expression of TRPV1 and TRPV4, thus restoring normal dietary behaviors and improving the overall quality of life. This system ultimately promotes collagen fiber deposition and accelerates the re-epithelialization of the ulcer wound, positioning DATS@Arg-EA-SA as a promising gas-delivery nanoplatform for rapid wound repair in the clinical treatment. Statement of Significance Oral mucosal wounds are highly susceptible to microbial infections, leading to inflammation, pain, delayed healing, and a significant decline in quality of life. We developed a multifunctional therapeutic nanoplatform (DATS@Arg-EA-SA) via the self-assembly of guanidinated dendritic peptides encapsulating the H 2 S donor DATS, which exhibited antibacterial, anti-inflammatory, and analgesic properties. In the oral ulcer microenvironment, DATS@Arg-EA-SA generates substantial NO under elevated ROS levels, while glutathione triggers the controlled release of H 2 S. NO disrupts bacterial membranes as the primary antibacterial agent, with H 2 S providing synergistic antibacterial effects. Furthermore, H 2 S and NO synergistically promote the transformation of M1 to M2 macrophages, attenuating inflammation. Importantly, the combined action of H 2 S and NO alleviates pain by downregulating TRPV1 and TRPV4, supporting the restoration of normal dietary behavior and improving quality of life.
研究领域:
药学
·
纳米技术
·
生物材料
·
医学
·
牙科
·
炎症研究
·
伤口愈合
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-21
·
IF 10.6
Chen Shang,He Yan,Huang Xin,Shen Yao,Zou Qingshuang,Yang Gun,Fu Li,Liu Quan,Luo Dixian
Tumor-associated macrophages (TAMs) are a promising target for cancer immunotherapy, but delivering therapeutic agents to TAMs within the tumor microenvironment (TME) is challenging. In this study, a photosensitive, dual-targeting nanoparticle system (M.RGD@Cr-CTS-siYTHDF1 NPs) was developed. The structure includes a shell of DSPE-modified RGD peptides targeting integrin receptors on tumor cells and carboxymethyl mannose targeting CD206 receptors on macrophages, with a core of chitosan adsorbing m6A reading protein YTHDF1 siRNA and chromium nanoparticles (Cr NPs). The approach is specifically designed to target TAM and cancer cells, utilizing the photothermal effect of Cr NPs to disrupt the TME and deliver siYTHDF1 to TAM. In experiments with tumor-bearing mice, M.RGD@Cr-CTS-siYTHDF1 NPs, when exposed to laser irradiation, effectively killed tumor cells, disrupted the TME, delivered siYTHDF1 to TAMs, silenced the YTHDF1 gene, and shifted the STAT3-STAT1 equilibrium by reducing STAT3 and enhancing STAT1 expression. This reprogramming of TAMs towards an anti-tumor phenotype led to a pro-immunogenic TME state. The strategy also suppressed immunosuppressive IL-10 production, increased expression of immunostimulatory factors (IL-12 and IFN-γ), boosted CD8 + T cell infiltration and M1-type TAMs, and reduced Tregs and M2-type TAMs within the TME. In conclusion, the dual-targeting M.RGD@Cr-CTS-siYTHDF1 NPs, integrating dual-targeting capabilities with photothermal therapy (PTT) and RNA interference, offer a promising approach for molecular targeted cancer immunotherapy with potential for clinical application. Graphical Abstract
研究领域:
癌症生物学
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纳米技术
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免疫疗法
·
分子生物学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
Bioactive Materials
·
2025
·
IF 20.3
Manxiang Wu,Dong Xie,Lianfu Wang,Zhusheng Liu,Hongying Bao,Tao Ye,Chengyuan Hong,Jie Lin,Tianxiang Chen,Aiguo Wu,Qiang Li
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation and progressive joint destruction. Its pathogenesis involves aberrant activation and aggressive proliferation of fibroblast-like synoviocytes (FLS), excessive macrophage infiltration, and disrupted M1/M2 macrophage polarization within the synovial microenvironment (SME). However, current therapies remain inadequate for precise SME modulation, often leading to limited efficacy and poor prognosis. To address this challenge, we developed a multifunctional nanocapsule, termed RP/HP@Mn/L, which is composed of a low molecular weight heparin (LMWH)-modified, Mn 2+ -doped hollow mesoporous polydopamine (HP) nanocarrier co-loaded with rapamycin (Rap) and paeoniflorin (Pae). This nanocapsule's dual-ligand strategy targets P-selectin on inflamed endothelial cells and integrin αM on inflammatory macrophages, enabling precise spatiotemporal accumulation at the pathological site. This nanocapsule enables spatiotemporally specific targeting of both inflammatory endothelial cells and inflammatory macrophages, thereby enhancing precise drug delivery to pathological sites. Mechanistic investigations revealed that RP/HP@Mn/L, in combination with mild photothermal therapy (PTT) mediated by HP, effectively suppressed FLS proliferation and invasion. Concurrently, it promoted the polarization of macrophages from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype. These synergistic effects facilitated the remodeling of the SME, thereby alleviating synovitis and enhancing bone repair in RA. In conclusion, this study proposes a spatiotemporally targeted combinatorial nanotherapeutic strategy that integrates multimodal mechanisms for SME modulation. This approach represents a promising therapeutic platform for improving outcomes in RA and other autoimmune disorders.
研究领域:
纳米医学
·
免疫治疗
·
风湿病学
·
生物医学工程
·
药物递送系统
·
炎症性疾病
·
自身免疫性疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Zili Guo,Tao Chen,Xuehuan Wen,Qiangchang Fu,Jiabin Lai,Jiajin Li,Jiayu Chen,Jie Weng,Wang Wen,Qihua Cao,Junxiong Zhu,Zhaoming Ye,Xiaohua Yu,Lifeng Jiang
Osteoarthritis (OA) pathogenesis is profoundly influenced by dysregulated immune dynamics, where persistent interleukin-17 (IL-17)/T helper 17 (Th17) cell mediated inflammation coordinates with failed regenerative processes to perpetuate joint destruction. Here, we unveil the role of myeloid-derived suppressor cells (MDSCs) as dual-phase regulators that paradoxically orchestrate both inflammatory escalation and tissue repair in OA progression. Intra-articular administration of MDSCs in OA mice amplified IL-17 dependent inflammatory cascades and chemokine-driven leukocyte recruitment, revealing a context-dependent pro-inflammatory phenotype. Unexpectedly, MDSC depletion failed to attenuate joint damage, implying their indispensable yet multifaceted role in OA pathogenesis. Mechanistically, MDSCs exhibited functional plasticity by upregulating arginase-1 to polarize M2 macrophages, fostering a regenerative niche alongside their inflammatory activity. To resolve this duality, we developed a bio-responsive hydrogel-microsphere system integrating transforming growth factor β1 (TGF-β1) and interleukin-1 β1 antibody (anti–IL-1β) loaded mesoporous silica nanoparticles (MSNs). This spatiotemporally controlled platform selectively suppressed MDSC-mediated Th17 cell expansion while harnessing their intrinsic capacity to drive M2 macrophage polarization and chondrogenesis. The resultant shift from a pro-inflammatory to pro-regenerative microenvironment significantly attenuated cartilage erosion and restored joint integrity in OA models. Our findings redefine MDSCs as bifunctional immune orchestrators in OA and establish precision biomaterial guided immune decoding as a paradigm-shifting therapeutic strategy. By engineering MDSC plasticity through antagonistic cytokine delivery, this work provides a blueprint for microenvironment remodeling in degenerative joint diseases.
研究领域:
免疫学
·
再生医学
·
生物材料
·
纳米医学
·
风湿病学
·
组织工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
·
2022
·
IF 6.064
Yaping Shan,Gang Chen,Qiqi Shi,Jiaxi Huang,Yaping Mi,Wenbo Zhang,Huifeng Zhang,Bing Jia
Prosthetic implants of expanded polytetrafluoroethylene (ePTFE) in the cardiovascular system have a high failure rate over the long term because of thrombosis and intimal hyperplasia. Although multiple surface modification methods have been applied to improve the anti-thrombotic and in situ endothelialization abilities of ePTFE, none have delivered outstanding results in vivo . Our previous study combined heparin/collagen multilayers and REDV peptides to modify ePTFE, and the in-vitro results showed that modification ePTFE with heparin/collagen-REDV can promote the cytocompatibility and antiplatelet property. This study illustrated the physical change, selective endothelial cells capture ability, and in vivo performance in further. The physical test demonstrated that this modification improved the hydrophilicity, flexibility and strength of ePTFE. A competition experiment of co-cultured endothelial cells and vascular smooth muscle cells verified that the heparin/collagen-REDV modification had high specificity for endothelial cell capture. A rabbit animal model was constructed to evaluate the in vivo performance of modified ePTFE implanted in the right ventricular outflow tract. The results showed that heparin/collagen-REDV modification was safe, promoted endothelialization, and successfully achieved regional anti-thrombosis without influencing body-wide coagulation function. The pathologic manifestations and mRNA expression pattern in tissues in contact with modified ePTFE indicated that this modification method may reduce M2-type macrophage infiltration and the expression of genes related to immune and inflammatory responses. The heparin/collagen-REDV modification may lower the incidence of complications related to ePTFE implantation and has good prospects for clinical use.
研究领域:
生物材料
·
心血管工程
·
组织工程
·
生物医学工程
·
免疫学
✓ 已验证
DOI
PubMed
高影响因子
BIOMATERIALS
·
2024
·
IF 12.8
Yuhuan Li,Jiayin Lv,Shuchen Liu,Zhuoran Wang,Yu Gao,Zheyuan Fan,Lei Huang,Jing Cui,Boya Zhang,Xinchen Liu,Zhuo Zhang,Te Liu,Daowei Li,Modi Yang
The role of pro-inflammatory macrophages (M1) in rheumatoid arthritis (RA) is significant, as they produce excessive cytokines. Targeting efferocytosis is a potential manner to repolarize M1 macrophages into pro-resolving M2 phenotype, which restores immune homeostasis by releasing anti-inflammatory mediators. In this study, liquid nitrogen-treated dead macrophages (DM) are employed to act as a dead cell-derived active targeted drug carrier for shikonin (SHK) and induce efferocytosis in M1 macrophages with the enhancement of SHK as an AMP-activated protein kinase (AMPK)-activator. The synergistic activation of AMPK leads to uncoupled protein 2 (UCP2) upregulation and reprograms M1 macrophages into M2 phenotypes by promoting oxidative phosphorylation. In the mouse model of collagen-induced arthritis, the intravenous administration of DM/SHK leads to a consistent transformation of M1 macrophages into the M2 phenotype within the infiltrative synovium. This transformation of macrophages results in the restoration of immune homeostasis in the synovium through an increase in the production of pro-resolving mediators. Additionally, it inhibits synovial proliferation and infiltration and provides protection against erosion of cartilage and bone. In summary, LNT-based DM serves as an active targeting drug carrier to M1 macrophages and also acts synergistically with SHK to target immunometabolism.
研究领域:
免疫学
·
药理学
·
风湿病学
·
炎症
·
药物递送系统
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Jun Zhang,Lei Su,Zhinan Liu,Jincheng Tang,Lichen Zhang,Ziang Li,Dong Zhou,Zhuo Sun,Kun Xi,Peirong Lu,Guohua Deng
Following an ocular chemical injury, the release of neutrophil extracellular traps (NETs) triggers an innate immune cascade fibrotic effect involving macrophages (Mø), which limits corneal repair. However, the interplay and mechanisms between NETs and macrophages, as well as the coordination between the innate immunity and corneal repair, remain challenging issues. Using a co-culture system, we report that chemical stimulation exacerbates the accumulation of reactive oxygen species (ROS) within the polymorphonuclear neutrophils, leading to NET formation and the activation of M2 macrophages, ultimately inducing pathological fibrosis of the ocular surface through the IL-10/STAT3/TGF-β1/Smad2 axis. Inspired by the locally formed acidic microenvironment mediated by innate acute inflammatory stimulation, we further integrate sericin with oxidized chitosan nanoparticles loaded with black phosphorus quantum dots (BPQDs) using Schiff base chemistry to construct a functional pH-responsive hydrogel. Following corneal injury , the hydrogel selectively releases BPQDs in response to the acidic environment, inhibiting the innate immune cascade fibrosis triggered by the PMN-ROS-NETs. Thus, corneal pathological fibrosis is alleviated and reshaping of the ocular surface takes place. These results represent a refinement of the mechanism of inherent immune effector cell interactions, and provide new research ideas for the construction of nano biomaterials that regulate pathological fibrosis.
研究领域:
生物材料
·
免疫学
·
眼科
·
组织工程
·
纳米技术
✓ 已验证
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2025
·
IF 19
Shuhui Chen,Xin Zhang,Guangbing Luo,Qiuyuan Zhao,Jie shen,Jiamian Zhan,Qing Xie,Shaofeng Hua,Honghao Hou,Yutong He,Xiaozhong Qiu
To overcome the limitations of current cardiac patches in comprehensively treating post-infarction ventricular remodeling, a paradigm-shifting orchestrated adhesive anisotropic/anti-adhesive isotropic Janus conductive patch (AGMM/PDP) integrated with mitochondria-targeted nanoparticles (MSNs/P/M) is introduced. The anisotropic AGMM layer enables suture-free tissue integration via covalent/non-covalent bonding, while the PDP layer forms a superhydrophilic antifouling barrier preventing postoperative adhesions. Simultaneously, MSNs/P/M nanoparticles achieve unprecedented mitochondrial salvage, leveraging polydopamine homing and melatonin synergy for enhanced mitochondrial affinity and efficient lysosomal escape, effectively preserving ultrastructure, membrane potential, and restoring oxidative phosphorylation to increase ATP production 1.8-fold under hypoxia. Therapeutically, this integrated system orchestrates synchronized multi-scale repair: acutely scavenging reactive oxygen species (ROS) (94% reduction), subsequently driving M1-to-M2 macrophage polarization to mitigate inflammation and stimulate angiogenesis (4.4-fold increased vascular density), and chronically restoring anisotropic conduction (55% increased velocity) and mechanical synchrony via transcriptomic reprogramming (upregulating energy/contractile genes; downregulating fibrosis/inflammation markers). This synergistically reversed ventricular remodeling in vivo, evidenced by 25% improved ejection fraction, 3.5-fold reduced fibrosis, and suppressed arrhythmias, collectively establishing a transformative. The developed patch presents a comprehensive Janus therapeutic strategy by mimicking the structural anisotropy native cardiac tissue while conferring mechanical isotropy, by inhibiting fibrosis, by restoring bioenergetics, which more effectively promotes cardiac functional recovery.
研究领域:
生物医学工程
·
心脏组织工程
·
纳米医学
·
再生医学
·
电生理学
·
线粒体生物学
·
生物材料
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）