JOURNAL OF CONTROLLED RELEASE
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2024
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IF 10.5
Baisong Li,Lin Ma,Xiwen Li,Zainab Suleman,Changming Liu,Olga Piskareva,Mi Liu
Precisely co-delivering antigens and immunosuppressants via nano/microcarriers to antigen-presenting cells (APCs) to induce antigen-specific immune tolerance represents a highly promising strategy for treating or preventing autoimmune diseases. The physicochemical properties of nano/microcarriers play a pivotal role in regulating immune function, with particle size and surface charge emerging as crucial parameters. In particular, very few studies have investigated micron-scale carriers of antigens. Herein, various nanoparticles and microparticles (NPs/MPs) with diverse particle sizes (ranging from 200 nm to 5 μm) and surface charges were prepared. Antigen peptides (MOG35–55) and immunosuppressants were encapsulated in these particles to induce antigen-specific immune tolerance. Two emulsifiers, PVA and PEMA, were employed to confer different surface charges to the NPs/MPs. The in vitro and in vivo studies demonstrated that NP/MP-PEMA could induce immune tolerance earlier than NP/MP-PVA and that NP/MP-PVA could induce immune tolerance more slowly and sustainably, indicating that highly negatively charged particles can induce immune tolerance more rapidly. Among the different sizes and charged particles tested, 200-nm-NP-PVA and 3-μm-MP-PEMA induced the greatest immune tolerance. In addition, the combination of NPs with MPs can further improve the induction of immune tolerance. In particular, combining 200 nm-NP-PVA with 3 μm-MP-PEMA or combining 500 nm-NP-PEMA with 3 μm-MP-PVA had optimal therapeutic efficacy. This study offers a new perspective for treating diseases by combining NPs with MPs and applying different emulsifiers to prepare NPs and MPs.
研究领域:
免疫学
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纳米技术
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药学
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生物医学工程
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DOI
PubMed
高影响因子
Materials Horizons
·
2025
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IF 10.7
Yubo Liu,Fangming Liang,Rui Zhang,Chengcheng Tang,Xin Li,Yongjun Wang,Zhonggui He,Hongzhuo Liu
Recombinant adeno-associated virus (AAV) vectors have become the promising platform to deliver a therapeutic transgene for the treatment of monogenic disorders. However, anti-AAV antibodies that are released by B cells after AAV treatment create a substantial barrier to their long-lasting safe and effective therapy, making AAV gene therapy a “one shot” treatment. Here, we offered that tolerogenic nano-adjuvants (named RICP) composed of rapamycin (RAPA) and itaconate (ITA), to induce specific immune tolerance to overcome the anti-drug antibodies (ADAs). Such strategy blocked the feedback loops of follicular helper T （Tfh） cells and germinal center B cells by metabolic regulation, complementary to induction of regulatory T cells (Tregs) by mTORc1 inhibitor RAPA, consequently abolished the secretion of anti-AAV antibodies. The developed nano-adjuvants can also significantly increase expression of a transgene (such as luciferase, green fluorescent protein and human embryonic alkaline phosphatase reporter transgene) in the liver at re-dosing, compared to mice treated with AAV alone which showed almost no change in transgene expression. The emerging strategy provided AAV re-administration schedule available for not only mitigate toxicities with high vector doses, but re-storing therapeutic benefits in children in significant cell proliferation.
研究领域:
基因治疗
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免疫学
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纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PLACENTA
·
2025
·
IF 2.5
Caiqun Huang,E Fen Cheng,Jinping Ni,Ying Lyu
Introduction Unexplained recurrent spontaneous abortion (URSA) involves multifactorial etiologies, with regulatory T cells (Tregs) playing a pivotal role in maintaining immune tolerance during pregnancy. Baicalein, a flavonoid from Scutellaria baicalensis, exhibits anti-inflammatory and immunomodulatory properties. This study evaluates baicalein's therapeutic potential in mitigating URSA via the TLR4/NF-κB signaling pathway. Methods A URSA mouse model was used, and baicalein was administered intraperitoneally. Pregnancy outcomes, abortion rates, and placental morphology were assessed on gestational day 14 (G14). Treg cells were quantified via flow cytometry, and gene/protein expression levels were analyzed by immunohistochemistry, Western blotting, and real-time PCR. In vitro experiments on ihESCs further investigated the role of the TLR4/NF-κB pathway. Results Baicalein reduced abortion rates from 33.3 % in URSA mice to 21.6 % (low dose) and 14.8 % (high dose), improved embryonic development by altering placental structure and decidual morphology, and reduced inflammation at the maternal-fetal interface. It expanded Treg cells and enhanced the expression of IGFBP-1 and PRL, markers of endometrial decidualization, and decreased TLR4, p-P65, and P65 expression. In vitro, baicalein's effects were abrogated by TLR4 inhibition, confirming pathway specificity. Discussion Baicalein improved pregnancy outcomes by enhancing Treg function and promoting decidualization via TLR4/NF-κB pathway inhibition. These findings highlight baicalein's potential as a therapeutic agent for URSA.
研究领域:
生殖医学
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免疫学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
ACS Nano
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2025
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IF 16
Shuo Wang,Yuequan Wang,Yantong Li,Xiaoxue Lai,Miao Hu,Meng Chen,Cong Li,Xinrong Liu,Yanzhi Song,Yihui Deng
Inflammation-related immune cell subsets with abnormal activation, impaired tolerance, and complex intercellular interactions drive the progression and incurability of autoimmune diseases (AIDs). Here, we present an antigen-free nanovaccine-enabled holo-immunotherapy that comprehensively modulates inflammation, innate immunity, and adaptive immunity. The nanovaccine, composed of dual NF-κB inhibitors (budesonide and bortezomib) and comodified with sialic acid (SA) and enzyme-cleavable polyethylene glycol (PEG), leverages the SA-Siglec axis for targeted delivery to inflammation-related macrophage, dendritic cell, and CD4+ T cell subsets. By bridging innate and adaptive immunity, this multitargeted strategy synergistically reshapes the inflammatory microenvironment, establishes robust memory immune tolerance, and promotes immune homeostasis restoration, leading to sustained efficacy and delayed relapse in the collagen-induced arthritis (CIA) mouse model. Unlike traditional vaccines, the antigen-free design eliminates reliance on exogenous antigens, minimizes off-target immune risks, and holds promise for broader clinical applicability. The nanovaccine outperforms anti-TNF-α antibodies in treating models of CIA, adjuvant-induced arthritis, and chronic ulcerative colitis, highlighting its potential as a universal vaccine platform for AID therapy. Overall, this work provides a strategy to address AID challenges through precise immune regulation and durable therapeutic benefits.
研究领域:
免疫学
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纳米医学
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转化医学
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自身免疫病治疗
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分子药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Hanfeng Qin,Junbin Gao,Wenxin Xu,Yanzhen Song,Ruotian Zhang,Hong Wang,Yicheng Ye,Jia Sun,Jiamiao Jiang,Haiying Liang,Ning Zhong,Hao Tian,Xiaodong Chen,Fei Peng,Yingfeng Tu
Current immunotherapeutic approaches for autoimmune disorders primarily rely on the use of generalized immunosuppressive medications. However, most immune drugs and tolerogenic immunomodulators are insufficient on their own to establish antigen-specific immunological tolerance (ASIT). Therefore, steering antigen-presenting cells (APCs) towards a tolerogenic state with minimal risk of broad immune suppression may be an effective approach. In pursuit of enhanced ASIT, magnetic nanoparticles cloaked with an erythrocyte membrane anchored with the model antigen ovalbumin have been successfully developed, allowing for the in vivo conversion of APCs into tolerogenic microrobots that respond to magnetic activation. Actuated by a rotating magnetic field (RMF), the in situ-formed cell-based microrobots can be guided to inflammatory sites, thereby augmenting systemic and local immune tolerance. These tolerogenic microrobots represent an innovative platform for active immunomodulation and provide precise control over the magnitude and direction of immune responses. This breakthrough offers new insights into the therapeutic management of allergies, autoimmune disorders, and the prevention of anti-drug antibodies in biologic therapies.
研究领域:
免疫学
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生物医学工程
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纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2024
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IF 4.8
Xiaoxue Cao,Zhaoran Wang,Yi Jiao,Wenya Diao,Qishun Geng,Lu Zhao,Zihan Wang,Xing Wang,Mengxiao Zhang,Jiahe Xu,Bailiang Wang,Tingting Deng,Cheng Xiao
Treg cell-based therapy has exhibited promising efficacy in combatting rheumatoid arthritis (RA). Dihydroartemisinin (DHA) exerts broad immunomodulatory effects across various diseases, with its recent spotlight on T-cell regulation in autoimmune conditions. The modulation of DHA on Treg cells and its therapeutic role in RA has yet to be fully elucidated. This study seeks to unveil the influence of DHA on Treg cells in RA and furnish innovative substantiation for the potential of DHA to ameliorate RA. To this end, we initially scrutinized the impact of DHA-modulated Treg cells on osteoclast (OC) formation in vitro using Treg cell-bone marrow-derived monocyte (BMM) coculture systems. Subsequently, employing the collagen-induced arthritis (CIA) rat model, we validated the efficacy of DHA and probed its influence on Treg cells in the spleen and popliteal lymph nodes (PLN). Finally, leveraging deep proteomic analysis with data-independent acquisition (DIA) and parallel accumulation-serial fragmentation (PASEF) technology, we found the alterations in the Treg cell proteome in PLN by proteomic analysis. Our findings indicate that DHA augmented suppressive Treg cells, thereby impeding OC formation in vitro. Consistently, DHA mitigated erosive joint destruction and osteoclastogenesis by replenishing splenic and joint-draining lymph node Treg cells in CIA rats. Notably, DHA induced alterations in the Treg cell proteome in PLN, manifesting distinct upregulation of alloantigen Col2a1 (Type II collagen alfa 1 chain) and CD8a (T-cell surface glycoprotein CD8 alpha chain) in Treg cells, signifying DHA's targeted modulation of Treg cells, rendering them more adept at sustaining immune tolerance and impeding bone erosion. These results unveil a novel facet of DHA in the treatment of RA.
研究领域:
免疫学
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风湿病学
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药理学
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蛋白质组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2024
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IF 5.3
Yingxi Zhang,Yuan Gao,Ning Li,Linyi Xu,Yongjun Wang,Hongzhuo Liu
Around 40 % of patients fail to achieve primary clinical outcomes for rheumatoid arthritis (RA). The growth of lymphatic system in the synovial membrane, is a primary response during RA inflammation. It is suggested that a delivery strategy targeting immunosuppressive agents to the synovial lymph nodes and then to the immune cells is beneficial for resolving arthritis. This study introduced a synthetic polypropylene sulfide methotrexate nano-delivery system (PPS-MTX), which was prepared by covalently bonding methotrexate to polypropylene sulfide, with a diameter size range of 36 nm. It enhanced joint accumulation and retention, which can be selectively uptake by antigen-presenting cells in the synovial lymphatic system. The results indicated that PPS-MTX nanoparticles effectively improved arthritis disease progression and restored the immune tolerance microenvironment in the synovial lymphatic system, promoting peripheral tolerance in collagen-induced arthritis mice. Additionally, no systemic toxicity was observed. This study presents a promising targeted strategy for inducing immune tolerance in the treatment of rheumatoid arthritis.
研究领域:
药学
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免疫学
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纳米技术
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风湿病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
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IF 8.2
Ni An,Guzailinuer Yasen,Ximu Li,Xianbao Shi,Yongjun Wang,Hongzhuo Liu
Alopecia areata (AA) is a prevalent autoimmune condition that causes sudden hair loss and poses significant psychological challenges to affected individuals. Current treatments, including corticosteroids and Janus kinase inhibitors, fail to provide long-term efficacy due to adverse effects and relapse after cessation. This study introduces a nanoparticle (NP) system that codeliver diphenylcyclopropenone (DPCP) and rapamycin (RAPA) prodrugs to induce immune tolerance and promote hair regeneration. The results demonstrated that the coassembled NPs exhibited uniformity and stability, were efficiently taken up by antigen-presenting cells (APCs), and successfully induced dendritic cells (DCs) to differentiate into tolerogenic phenotypes in vitro. In vivo studies on a mouse model of alopecia showed that these NPs significantly accelerated the transition of hair follicles from the telogen phase to the anagen phase, promoting hair regrowth. This research presents a promising therapeutic strategy for AA and offers insights into treating autoimmune diseases where autoantigens are unclear.
研究领域:
免疫学
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皮肤科
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药学
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自身免疫疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
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2021
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IF 12.479
Liangliang Dai,Xiang Li,Xinmin Zheng,Zhenxiang Fu,Mengjiao Yao,Siyu Meng,Jiangong Zhang,Binbin Han,Quanli Gao,Jing Chang,Kaiyong Cai,Hui Yang
Immunosuppressive tumor microenvironment and low delivery efficiency severely impede the tumor chemotherapy effect. To address this issue, we develop a pH/ROS cascade-responsive prodrug micelle to deliver siTGF-β with size-shrinkage and charge-reversal property, leading to synergistical tumor microenvironment remodeling. The nanosystem highly improved endocytosis efficiency and tumor penetration depth through charge reversal and size reduction upon exposure to weakly acidic tumor microenvironment. Moreover, the nanocarrier would rapidly escape from endo/lysosome, disassemble and release siTGF-β and hydroxycamptothecin in response to high intracellular ROS. Furthermore, the nanosystem significantly boosted antitumor immune response and reduced immune tolerance with remodeling tumor microenvironment, which significantly prolonged the survival time of tumor-bearing mice (75% survival rate upon 35 days). It is realized by the combined effects of chemotherapy-enhanced immunogenicity and recruitment of effector T cells , TGF-β-blockade immunotherapy-activated inhibition immunosuppressive tumor microenvironment and epithelial-to-mesenchymal transition (EMT), and regulation physical tumor microenvironment via reducing the dense tumor extracellular matrix and the high tumor interstitial pressure obstacles. To this end, the nanosystem not only overcame biobarriers and reinforced antitumor immune response, but also effectively inhibited tumor growth, metastasis and recurrence in vivo .
研究领域:
肿瘤学
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药学
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纳米技术
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2024
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IF 12.8
Guoquan Wu,Tianyu Su,Peng Zhou,Rongze Tang,Xu Zhu,Jin Wang,Minghao Chao,Liying Fan,Hanrong Yan,Peng Ye,Dehong Yu,Fenglei Gao,Hongliang Chen
Nanomedicines for immune modulation have made advancements in the treatment of rheumatoid arthritis (RA). However, due to aberrations in patients' immune systems, inducing antigen-specific immune tolerance while halting disease progression remains a significant challenge. Here, we develop a highly targeted multifunctional nanocomplex, termed M2Exo@CuS-CitP-Rapa (M2CPR), with the aim of selectively inhibiting inflammatory immune reactions while promoting immune tolerance towards specific antigens. M2CPR specifically targets inflammatory tissues in RA, delivering CuS NPs, CitP, Rapa, and endogenous anti-inflammatory factors, thereby ameliorating the inflammatory joint microenvironment. CuS NPs induce Cuproptosis of activated T cells, whose fragments are engulfed by resident or recruited macrophages, resulting in abundant production of TGF-β. TGF-β acts synergistically with Rapa to induce the iDCs into tDCs. tDCs present CitP to Naive T cells, promoting Tregs differentiation. Tregs, in turn, produce more TGF-β, inducing tDCs differentiation, thereby establishing a cycle of immune tolerance. Through in vitro and in vivo experiments, we validate that M2CPR can induce robust and durable antigen-specific immune tolerance, offering a new paradigm for RA therapy.
研究领域:
免疫学
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纳米技术
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风湿病学
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Advanced Research
·
2024
·
IF 11.4
Chunhua Huang,Cheng Lyu,Heung-Lam Mok,Yiqi Xu,Ka-Wing Cheng,Cheng Zhang,Die Hu,Lin Zhu,Chengyuan Lin,Xin Chen,Hor-Yue Tan,Zhaoxiang Bian
Introduction Ulcerative colitis (UC) is a chronic inflammatory disease characterized by loss of immune tolerance to luminal antigens and progressive intestinal tissue injury. Thus, the re-establishment of immune tolerance is crucial for suppressing aberrant immune responses and UC progression. Objectives This study aimed to investigate the mechanisms underlying the action of CDD-2103 and its bioactive compounds in mediating immune regulation in mouse models of colitis. Methods Two experimental colitis models, chronic 2,4,6-trinitrobenzene sulfonic acid (TNBS)- and T-cell transfer-induced Rag1 -/- mice, were used to determine the effects of CDD-2103 on colitis progression. Single-cell transcriptome analysis was used to profile the immune landscape and its interactions after CDD-2103 treatment. Liquid chromatography-mass spectrometry (LC-MS) was used to analyze the major components interacting with lymphoid cells. A primary cell co-culture system was used to confirm the effects of bioactive component. Results CDD-2103 dose-dependently suppresses the progression of colitis induced by chemicals or T cell transplantation in Rag1 -/- mice. The effect of CDD-2103 is primarily attributable to an increase in the de novo generation of regulatory T cells (Tregs) in the lamina propria (LP). Single-cell transcriptomic analysis revealed that CDD-2103 treatment increased the number of tolerogenic dendritic cells (DCs). Mechanistically, CDD-2103 promoted tolerogenic DCs accumulation and function by upregulating several genes in the electron transport chain related to oxidative phosphorylation, leading to increased differentiation of Tregs. Further LC-MS analysis identified several compounds in CDD-2103, particularly those distributed within the mesenteric lymph nodes of mice. Subsequent studies revealed that palmatine and berberine promoted tolerogenic bone marrow-derived dendritic cells (BMDC)-mediated Treg differentiation. Conclusion Overall, our study demonstrated that the clinically beneficial effect of CDD-2103 in the treatment of UC is based on the induction of immune tolerance. In addition, this study supports berberine and palmatine as potential chemical entities in CDD-2103 that modulate immune tolerance.
研究领域:
免疫学
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药理学
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胃肠病学
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分子生物学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2023
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IF 10.8
Yanyun Hao,Hui Li,Xiaoyan Ge,Yang Liu,Jialin Yin,Xia Li,Yutong Liu,Hongfei Chen,Lingling Huang,Jing Zou,Shiying Zhang,Hao Wu,Zhiyue Zhang
Immunotherapy has fundamentally altered cancer treatment; however, its effectiveness is clinically hampered by insufficient intratumoral T lymphocyte infiltration and failed T lymphocyte priming. Additionally, inducing cancer-specific immune responses while sparing normal cells remains challenging. Herein, we developed a redox-activatable polymeric nanoswitch (c-N@IM/JQ) that remained ‘off’ status in circulation but rapidly switched ‘on' after entering the tumor. Toll-like receptor (TLR) 7/8 agonist (imidazoquinoline, IMQ) and bromodomain and extraterminal inhibitor (JQ1) are locked in c-N@IM/JQ with a redox-cleavable linker (switch off). Upon systemic administration , c-N@IM/JQ with c-RGD peptide modification preferentially accumulated at tumor sites and responded to the high glutathione levels to release native IMQ for fully mobilizing T lymphocyte army, and JQ1 for removing the programmed death ligand (PD-L)-1 protection on tumor cells (switch on). These strengthened T lymphocyte armies are easily accessible to these de-protected tumor cells, revitalizing the immune response against tumors.
研究领域:
癌症免疫疗法
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纳米技术
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药学
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分子生物学
✓ 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）