ANALYST
·
2018
·Vol. 143
·期 19
·4630-4637
·
IF 3.864
Guolan Tian,Lan Chen,Renxiao Liu,Guanglu Ge
Quantitative analysis using surfactant–particles interaction is the basis for many applications. In situ measurements of surfactant adsorption on nanoparticles are important to understanding adsorption kinetics. However, it is quite difficult to determine the individual numbers for each monomodal particles in a multimodal mixture system by current technologies. To cope with this problem, a new method, i.e. 2D differential centrifugal sedimentation (2D-DCS), has been developed and applied in situ to measure the number of CTAB molecules adsorbed on the surface of silica particles, assuming that the adlayer is composed of a compact CTAB monolayer. Results show that 2D-DCS can measure the adsorption amount for particles not only with single size distribution but also with multiple size distributions. The number of adsorbed CTAB per nm2 on silica particles determined by 2D-DCS are 1.4 and 3.9 for the monomodal particles of 210 and 1000 nm, respectively, which is similar to that measured by ζ-potential, DLS and UV-vis spectrometry, and 1.4, 2.3 and 2.5 for 210, 430 and 700 nm particles, respectively, for a trimodal particle system, where the size-dependent adsorption is difficult to be simultaneously measured by other technologies.
研究领域:
化学
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材料科学
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分析化学
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DOI
PubMed
高影响因子
PHARMACOLOGICAL RESEARCH
·
2022
·
IF 10.334
Yuhang Li,Yitian Li,Sennan Xu,Yue Chen,Pan Zhou,Ting Hu,Hua Li,Ying Liu,Yaping Xu,Jie Ren,Yan Qiu,Canzhong Lu
Psoriasis is an incurable autoimmune disease that affects 2–3% of the world’s population. Limited understanding of its pathogenesis hinders the development of therapies for the disease. Herein, we reported that N-acylethanolamine acid amidase (NAAA), a cysteine enzyme that catalyzes the hydrolysis of fatty acid ethanolamides (FAEs), was upregulated in psoriasis patients and imiquimod (IMQ)-induced mouse model of psoriasis. The upregulated NAAA contributes to the progression of psoriasis via enhancing dendritic cell (DCs) maturation. Transgenic expression of NAAA in mice accelerated the development of psoriasis, whereas genetic ablation of NAAA or local administration of NAAA inhibitor F96 ameliorated psoriasis. NAAA expressed in dendritic cells (DCs), but not in macrophages, T cells, or keratinocytes plays a critical role in psoriasis development. In addition, the results showed that NAAA degrades palmitoylethanolamide (PEA) and reduces PEA-PPARα-mediated dissociation of NF-κB p65 from Sirtuin 1 (SIRT1), subsequently, repressing the acetylation of p65 and down-regulating IL10 production. The decreased IL10 then leads to the maturation of DCs, thus promoting the development of psoriasis. These results provide new insights into the pathophysiological mechanism of psoriasis and identify NAAA as a novel target for the treatment of psoriasis.
研究领域:
免疫学
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皮肤病学
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药理学
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DOI
PubMed
高影响因子
Bioactive Materials
·
2022
·
IF 16.874
Wenxin Qi,Naijun Dong,Lingling Wu,Xueqi Zhang,He Li,Hao Wu,Natalie Ward,Jian Yu,He Liu,Jiao Wang,Xiaoyong Deng,Robert Chunhua Zhao
The high occurrence rate and difficulties in symptom control are listed as the major problems of oral mucosal disease by medical professionals. Following the development of oral mucosal lesions, the oral microenvironment changes, immunity declines, and continuous bacterial stimulation causes wound infection. Traditional antibacterial drugs are ineffective for oral mucosal lesions. To overcome this problem, a light-responsive antibacterial hydrogel containing sustained-release BMSCs was inspired by the trauma environment in the oral cavity, which is different from that on the body surface since it mostly remains under dark conditions. In the absence of light, the hydrogel seals the wound to form a barrier, exerts a natural bacteriostatic effect, and prevents invasion by foreign bacteria. Simultaneously, mesenchymal stem cells are presented, and the released growth factors and other substances have excellent anti-inflammatory and angiogenic effects, which result in rapid repair of the damaged site. Under light conditions, after photo-induced shedding of the hydrogel, RuB 2 A exerts an antibacterial effect accompanied by degradation of the hydrogel. Results in a rat oral mucosal repair model demonstrate that DCS-RuB 2 A 2 -BMSCs could rapidly repair the oral mucosa within 4 days. Sequencing data provide ideas for further analysis of the intrinsic molecular mechanisms and signaling pathways. Taken together, our results suggest that this light-responsive antibacterial hydrogel loaded with BMSCs can be used for rapid wound repair and may advance the development of therapeutic strategies for the treatment of clinical oral mucosal defects.
研究领域:
生物医学工程
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组织工程
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口腔医学
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干细胞研究
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DOI
PubMed
高影响因子
Scientific Reports
·
2024
·Vol. 14
·期 1
·1-13
·
IF 3.8
Yao Fei,Yuan Qin,Yan Yichao,Liang Guoqiang,Zhou Liang,Xu Heng,Gao Shaomei,Zou Ting,Zhang Lurong
Yu-Ping-Feng-San (YPF) is a famous classical Chinese medicine formula known for its ability to boost immunity. YPF has been applied to enhance the immune status of tumor patients in clinical practice. However, there is still a lack of research on its immune regulatory effects and mechanisms in the tumor microenvironment. This study was designed to investigate the effects and mechanism of YPF on improving the immune suppression state of hepatocellular carcinoma (HCC) microenvironment. In an orthotopic mouse model of HCC, YPF improved the immune microenvironment of HCC immunosuppression, enhanced the maturation of dendritic cells (DCs), promoted the release of IL-12, and decreased the presence of JAK2, p-JAK2, STAT3, and p-STAT3 proteins in both tumor tissue and paracancerous tissues. YPF also could promote the maturation and reduce the activation of JAK2, p-JAK2, STAT3, and p-STAT3 proteins of mouse bone marrow-derived DCs induced by culture medium or tumor supernatant in vitro . Transient transfection of siRNA-STAT3 with DCs resulted in an increase in its maturation and its secretion of IL-12. On the whole, these combined effects of YPF served to ameliorate the HCC immune suppression microenvironment, which conducive to immune cells play the role of immune surveillance and killing liver cancer cells. The mechanisms of these combined effects were, at least in part, related to its inhibition of the activated JAK2-STAT3 signaling pathway in DCs within the HCC microenvironment.
研究领域:
肿瘤学
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免疫学
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药理学
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DOI
PubMed
高影响因子
VIROLOGY
·
2026
·
IF 2.6
Qi Liao,Yi-Ge Luo,Jing-Long Ye,Zhi-Yuan Shi,Xu-Meng Feng,Hai-Tao Lu,Hang-Yu Zhou,Junyu Wu,Zhong-Yu Liu
Multiple studies have reported that different clades or strains of Zika virus (ZIKV) replicated with varied efficiency in cell culture. However, the molecular basis of these differences remains unclear. In this study, it was first shown that the d ownstream of the 5′- c yclization s equence p seudo k not (DCS-PK) is required for efficient viral RNA (vRNA) replication of ZIKV, similar to its function in dengue virus life-cycle by using a newly developed ZIKV replicon. Interestingly, a combination of phylogenetic analysis, RNA chemical probing, and structure prediction revealed that substitutions were accumulated in the DCS-PK sequence and its structural integrity was improved during the evolutionary history of ZIKV. By using replicons of representative strains, it was demonstrated that the more stable DCS-PK from the Asian ZIKV strains was more potent in promoting vRNA replication in comparison with the less stable version found only in the early-diverged African strains. The significance of this difference was further supported by the characterization of virus mutants generated by reverse genetics approaches. MR766 mutants harboring a stabilized DCS-PK exhibited a moderate advantage over the corresponding wild type controls in replication fitness, which was detected by direct competition and reporter virus assays. Moreover, introducing a metastable DCS-PK into the Asian FSS13025 strain attenuated viral replication in multiple in vitro models, including human neural stem cells. In summary, our work pointed to a structural adaptation of DCS-PK to enhance ZIKV replication fitness, highlighting an important role of cis -acting RNA elements in natural selection and virus evolution.
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高影响因子
Nanoscale
·
2025
·
IF 5.1
Sha Liu,Lina Wang,Yupeng Wang,Lina Geng
Delayed healing of post-melanoma-resection wounds is prone to induce tumor recurrence. Therefore, postoperative wound management for tumor resection needs concurrently address anti-cancer activity and wound healing promotion. In this study, a multifunctional micelle-hydrogels (AB@MH) was fabricated by integrating reactive oxygen species (ROS)-responsive nanomicelles, which co-loaded with apigenin and BMS-202, into dodecyl-modified chitosan (DCS) based hydrogel via Schiff base linkages and hydrogen bonding interactions, for post-resection melanoma therapy. This micelle-hydrogel enables ROS-triggered drug release, thereby minimizing systemic toxicity. More importantly, the released apigenin exerts selective cytotoxicity against tumor cells and bacteria while inducing immunogenic cell death (ICD). When combined with co-released BMS-202, the formulation enhances anti-tumor efficacy without harming normal tissue cells. Moreover, the AB@MH is fabricated via a straightforward, crosslinker-free method, ensuring excellent biocompatibility and effective wound healing promotion. In the melanoma resection model, the AB@MH group exhibited marked suppression of tumor recurrence and accelerated wound repair. This work successfully integrates post-resection antitumor therapy and wound healing enhancement, achieving both safety and efficacy in postoperative cancer therapy.
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PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2025
·
IF 11.5
Ya Chu,Luyao Wang,Xi Huang,Cenxi Lao,Lin Luo,Jingyi Chen,Fangfei Jin,Lili Zhao,Kaiyuan Hu,Miao Lv,Xianjing Li,Yong Yang,Weijun Zhao,Wenguang Wang
The major challenge for in-situ cancer vaccines is to activate the DCs within the immunosuppressive tumor to initiate tumor-specific immune responses. By contrast, oncolytic viruses can always activate intratumoral DCs to initiate virus-specific immunity to eliminate viruses which will in turn reduce the anti-tumor effect of these viruses. To bridge the two approaches, we developed virus-mimicking nanoparticles (V-mimics) through self-assembly of artificial cyclic gadolinium-based GAMP (c·Gd·GAMP, a STING agonist), double-stranded RNA analog (Poly I: C), and indocyanine green (ICG). Within the V-mimics, c·Gd·GAMP and Poly I: C can simulate the DNA and RNA produced by virus replication to reverse the inhibition of the immunosuppressive tumor microenvironment on DCs by promoting the IFN-β secreting via activating nucleic acid sensors, thereby eliciting anti-tumor immune response in a manner akin to the immune response triggered by viruses. Notably, the V-mimics significantly promoted IFN-β secretion, enhanced DC maturation, and elicited robust tumor-specific immune memory when combined with photothermal therapy. In multiple tumor models, significant tumor inhibition was observed, including a metastasis and recurrence model. Therefore, leveraging the virus-mimicking particles to simulate the mechanism of virus-initiated specific immune responses to activate the intratumoral dendritic cells may open up new strategies for in-situ cancer vaccines.
研究领域:
肿瘤学
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免疫学
·
纳米医学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Changwei Zhang,Qinghui Cao,Yuanyu Li,Juan Lu,Sidong Xiong,Yan Yue
The induction of a robust CD8 + T cell response is critical for the success of an antiviral vaccine. In this study, we incorporated a STING agonist (SA) 2′3’-cGAMP into a previously developed exosome-based CVB3 viral myocarditis vaccine (Exo-VP1) to enhance its ability to induce CD8 + T cell responses and immunoprotection. Our results showed that compared to free SA adjuvant, exosome-mediated co-delivery (Exo SA -VP1) significantly enhanced SA uptake by dendritic cells (DCs) and more potently stimulated DC maturation. Immunization of mice showed that the Exo SA -VP1 vaccine-induced higher levels of CVB3-specific T cell proliferation and cytotoxicity, significantly increased the percentage of IFN-γ + CD8 + rather than CD4 + T cells, effectively reduced cardiac viral loads, attenuated myocarditis and improved survival in mice compared to the previous Exo-VP1 vaccine. Further investigation showed that Exo SA -VP1 significantly increased both the percentage and antigen cross-presentation capacity of splenic CD8 + DCs. Depletion of these CD8 + DCs by cytochrome C administration nearly abolished the advantage of Exo SA -VP1 in dominantly inducing IFN-γ + CD8 + cytotoxic T lymphocyte (CTL) production in immunized mice. Taken together, our results demonstrated the potential of Exo SA -VP1 as a promising candidate for anti-CVB3 vaccines and provide insights into immune-enhancing strategies aiming at augmenting antigen cross-presentation by DCs and enhancing potent CTL responses.
研究领域:
免疫学
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病毒学
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药学
·
分子生物学
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DOI
PubMed
高影响因子
Cancer Nanotechnology
·
2023
·Vol. 14
·期 1
·1-19
·
IF 5.7
Wu Yueyao,Wang Runtian,Shen Peiliang,Zhou Weijia,Chen Chao,Yang Kaiyong,Yang Jingjing,Song Yujun,Han Xin,Guan Xiaoxiang
Cancer treatment by inducing tumor cell immunogenic cell death (ICD) is critical for tumor therapy. However, ICD activation by single pathway is often limited in practical application due to its low efficiency. In addition, the low pH and anoxic microenvironments in solid tumors greatly limit the effective activation of ICD. Herein, hollow manganese dioxide (H-MnO2) nanomaterials were selected to load both Mitoxantrone (MTZ) and Chlorin e6 (Ce6) due to its hollow structure and ability to release drugs in the acidic environments. Thus, the synergy of photodynamic therapy (PDT), photothermal therapy (PTT) and chemotherapy can induce the process of immunogenic cell death, stimulate the maturation of dendritic cells (DCs), and activate the immune response to kill tumor cells dramatically. Efficient immunotherapeutic effects were obtained when MnO2-C/M-HA was given intravenously to 4T1 tumor-bearing BALB/c mice with 660 nm near-infrared laser irradiation. This study overcame the limitations of monotherapy and provided a multifunctional platform for tumor immunotherapy.
研究领域:
癌症治疗
·
纳米技术
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免疫学
·
药物递送系统
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产品关联
DOI
高影响因子
MOLECULAR PHARMACEUTICS
·
2021
·
IF 4.939
Chao Li,Yao Lu,Lili Cheng,Xiaoge Zhang,Jun Yue,Jie Liu
As a noninvasive therapy, high-intensity focused ultrasound (HIFU) shows great potential in inducing anticancer immune responses. However, the overall anticancer efficacy of HIFU is still limited due to the rapid attenuation of ultrasound waves and inadequacy of ultrasound waves to spread to the whole tumor. Here, we combined HIFU with the ultrasound contrast agent/chemotherapeutic drug co-delivery nanodroplets to achieve synergistic enhancement of anticancer efficacy. Different from the widely used thermal HIFU irradiation, by which excessive heating would result in inactivation of immune stimulatory molecules, we used short acoustic pulses to trigger HIFU (mechanical HIFU, mHIFU) to improve anticancer immune responses. The nanodroplets displayed a mHIFU/glutathione (GSH)-dual responsive drug release property, and their cellular uptake efficacy and toxicity against cancer cells increased upon mHIFU irradiation. The generated immunogenic debris successfully induced the exposure of damage-associated molecular patterns on the cell surface for dendritic cells (DCs) maturation. In vivo experiments with tumor-bearing mice showed that the co-delivery nanodroplets in combination with mHIFU could effectively inhibit tumor growth by inducing immunogenic cell death, activating DCs maturation, and enhancing the effector T-cell infiltration within tumors. This work reveals that combined treatment with nanodroplets and mHIFU is a promising approach to eradicate tumors.
研究领域:
肿瘤学
·
生物医学工程
·
免疫治疗
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DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
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
·
皮肤科
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药学
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自身免疫疾病
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DOI
PubMed
高影响因子
Small
·
2021
·Vol. 18
·期 1
·2105530
·
IF 13.281
Xiaofang Zhong,Guangsheng Du,Xuanyu Wang,Yangsen Ou,Hairui Wang,Yining Zhu,Xinyan Hao,Zhiqiang Xie,Yuandong Zhang,Tao Gong,Zhirong Zhang,Xun Sun
Parenteral vaccines typically can prime systemic humoral immune response, but with limited effects on cellular and mucosal immunity. Here, a subcutis-to-intestine cascade for navigating nanovaccines to address this limitation is proposed. This five-step cascade includes lymph nodes targeting, uptaken by dendritic cells (DCs), cross-presentation of antigens, increasing CCR9 expression on DCs, and driving CD103 + DCs to mesenteric lymph nodes, in short, the LUCID cascade. Specifically, mesoporous silica nanoparticles are encapsulated with antigen and adjuvant toll-like receptor 9 agonist cytosine-phosphate-guanine oligodeoxynucleotides, and further coated by a lipid bilayer containing all-trans retinoic acid. The fabricated nanovaccines efficiently process the LUCID cascade to dramatically augment cellular and mucosal immune responses. Importantly, after being vaccinated with Salmonella enterica serovar Typhimurium antigen-loaded nanovaccine, the mice generate protective immunity against challenge of S. Typhimurium . These findings reveal the efficacy of nanovaccines mediated subcutis-to-intestine cascade in simultaneously activating cellular and mucosal immune responses against mucosal infections.
研究领域:
免疫学
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纳米技术
·
疫苗研发
·
传染病
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）