RSC Advances
·
2016
·Vol. 6
·期 11
·8729-8735
·
IF 3.289
Suyan Wang,Limin Wang,Hongfu Chen,Yulong Wang,Jia Cai,Mingming Yang,Fengquan Liu
Here, a specific anti-Hg2+ monoclonal antibody (mAb) was generated and an eco-friendly immunochromatographic test strip (EFITS) based on a mAb-nanogold probe for rapid and specific detection of Hg2+ in water was developed. In the method, the conjugation of Hg–MNA (6-mercaptonicotinic acid)–BSA (bovine serum albumin) was synthesized as an immunogen, the conjugation of MNA–OVA (ovalbumin) was synthesized and selected as a coating antigen. The specific anti-Hg2+ mAb from BALB/C female mice was screened based on a competitive immunoassay. The coating antigen and goat anti-mouse IgG antibody were coated on a nitrocellulose membrane (NC membrane) as a test line and a control line, respectively. The anti-Hg2+ mAb-nanogold probe was applied to the conjugate pad. Hg2+ competes with OVA–MNA for the mAb-nanogold probe causing a color change on the test line corresponding to the Hg2+ content. Thus, we can distinguish the subtle differences through a strip reader. The resulting EFITS is able to detect Hg2+ with LOD of 0.4 ng mL−1 at 9 min by quantitative analysis. EFITS demonstrated here is eco-friendly (without Hg2+ on the strip), capable of rapid detection, and does not require chelators.
研究领域:
环境科学
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分析化学
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生物技术
·
毒理学
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产品关联
DOI
高影响因子
BIOMATERIALS
·
2019
·
IF 10.273
Jun Xu,Hui Wang,Ligeng Xu,Yu Chao,Chenya Wang,Xiao Han,Ziliang Dong,Hong Chang,Rui Peng,Yiyun Cheng,Zhuang Liu
Cancer vaccines for prevention and treatment of tumors have attracted tremendous interests as a type of cancer immunotherapy strategy. A major challenge in achieving robust T-cell responses to destruct tumor cells after vaccination is the abilities of antigen cross-presentation for antigen-presenting cells (APCs) such as dendritic cells (DCs). Herein, we demonstrate that a polyamidoamine dendrimer modified with guanidinobenzoic acid (DGBA) could serve as an effective protein carrier to enable delivery of protein antigen, thereby leading to effective antigen cross-presentation by DCs. With ovalbumin (OVA) as the model antigen and unmethylated cytosine-guanine dinucleotides (CpG) as the adjuvant, a unique type of tumor vaccine is formulated. Importantly, such DGBA-OVA-CpG nanovaccine can induce robust antigen-specific cellular immunities and further demonstrates outstanding prophylactic efficacy against B16-OVA melanoma. More significantly, the nanovaccine shows excellent therapeutic effect to treat established B16-OVA melanoma when used in combination with the programmed cell death protein 1 (PD-1) checkpoint-blockade immunotherapy. This study presents the great promises of employing rationally engineered cytosolic protein carriers for the development of tumor vaccines to achieve effective cancer immunotherapy.
研究领域:
癌症免疫学
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纳米技术
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疫苗学
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肿瘤生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Pharmaceutica Sinica B
·
2022
·
IF 14.903
Yunting Zhang,Min Jiang,Guangsheng Du,Xiaofang Zhong,Chunting He,Ming Qin,Yingying Hou,Rong Liu,Xun Sun
The rise of nanotechnology has opened new horizons for cancer immunotherapy. However, most nanovaccines fabricated with nanomaterials suffer from carrier-related concerns, including low drug loading capacity, unpredictable metabolism, and potential systemic toxicity, which bring obstacles for their clinical translation. Herein, we developed an antigen self-assembled nanovaccine, which was resulted from a simple acryloyl modification of the antigen to induce self-assembly. Furthermore, a dendritic cell targeting head mannose monomer and a mevalonate pathway inhibitor zoledronic acid (Zol) were integrated or absorbed onto the nanoparticles (denoted as MEAO-Z) to intensify the immune response. The synthesized nanovaccine with a diameter of around 70 nm showed successful lymph node transportation, high dendritic cell internalization, promoted costimulatory molecule expression, and preferable antigen cross-presentation. In virtue of the above superiorities, MEAO-Z induced remarkably higher titers of serum antibody, stronger cytotoxic T lymphocyte immune responses and IFN- γ secretion than free antigen and adjuvants. In vivo , MEAO-Z significantly suppressed EG7-OVA tumor growth and prolonged the survival time of tumor-bearing mice. These results indicated the translation promise of our self-assembled nanovaccine for immune potentiation and cancer immunotherapy.
研究领域:
癌症免疫学
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纳米技术
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药学
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免疫疗法
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE & TECHNOLOGY
·
2023
·
IF 10.9
Yike Hou,Zhe Tang,Jabeen Farheen,Madiha Saeed,Lijia Luo,Wenzi Ren,Dandan Luo,Asim Mushtaq,Ruibo Zhao,Jian Ge,Zhangsen Yu,Yao Li,M. Zubair Iqbal,Xiangdong Kong
Vaccine-based cancer immunotherapy has demonstrated a significant potential for cancer treatment in clinics. Although the efficiencies of vaccines are limited, they can be enhanced by a well-designed antigen delivery system that promotes sufficient antigen presentation of dendritic cells (DCs) for initiating high T cell immunity. Herein, antigen-loaded manganese oxide (Mn 3 O 4 ) triangular-shaped ultrasmall nanoparticles were prepared to stimulate DC-based immunotherapy under the guidance of T 1 magnetic resonance imaging. The FDA-approved triblock copolymer Pluronic® F-68 was used not only to transfer the phase from hydrophobic to hydrophilic but also to enrich antigen loading and improve the biocompatibility of the prepared nanoparticles. Ovalbumin (OVA), a model antigen, was adsorbed on the surface of polymer-coated nanoparticles through electrostatic interaction to form Mn 3 O 4 @PF68-OVA nanoparticle-antigen complexes to stimulate DC-based immunization and antigen-specific T cell immunity. The Mn 3 O 4 @PF68-OVA nanovaccine (NV) induces negligible toxicity effects against 4T1 and bone marrow-derived dendritic cells (BMDCs) by conventional methods supports the proliferation of intestine organoids, which are an innovative three-dimensional cytotoxicity evaluation system, thereby indicating their potential safety for in vivo cancer therapies. The designed paramagnetic nanovaccine possessed excellent OVA delivery to dendritic-regulated antigen-specific T cells in vitro by stimulating the maturation level of BMDCs. In addition, Mn 3 O 4 @PF68-OVA NVs enhance immunity in vivo by increasing the T-cells and M1 macrophages, which suggests improved immunity. Excitingly, vaccination with Mn 3 O 4 @PF68-OVA offer complete protection in the prophylactic group and significant tumor inhibition in the therapeutic group against B16-OVA tumor. In addition, the designed nanovaccine demonstrated high T 1 -MR imaging in the tumor, further justifying enhanced tumor accumulation and capability to real-time monitor the treatment procedure. This study presents a promising nanosystem to design an effective nanovaccine for T 1 -MR imaging-guided tumor immunotherapy.
研究领域:
癌症免疫治疗
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纳米技术
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免疫学
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磁共振成像
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生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Xiao-Lu Jie,Zi-Rui Luo,Jin Yu,Zhe-Ren Tong,Qiao-Qiao Li,Jia-Hui Wu,Yi Tao,Pei-Shi Feng,Ji-Ping Lan,Ping Wang
Ethnopharmacological relevance Pi-Pa-Run-Fei-Tang (PPRFT) is an empirical TCM prescription for treating asthma. However, the underlying mechanisms of PPRFT in asthma treatment have yet to be elucidated. Recent advances have revealed that some natural components could ameliorate asthma injury by affecting host metabolism. Untargeted metabolomics can be used to better understand the biological mechanisms underlying asthma development and identify early biomarkers that can help advance treatment. Aim of the study The aim of this study was to verification the efficacy of PPRFT in the treatment of asthma and to preliminarily explore its mechanism. Materials and methods A mouse asthma model was built by OVA induction. Inflammatory cell in BALF was counted. The level of IL-6, IL-1β, and TNF-α in BALF were measured. The levels of IgE in the serum and EPO , NO , SOD , GSH-Px, and MDA in the lung tissue were measured. Furthermore, pathological damage to the lung tissues was detected to evaluate the protective effects of PPRFT. The serum metabolomic profiles of PPRFT in asthmatic mice were determined by GC-MS. The regulatory effects on mechanism pathways of PPRFT in asthmatic mice were explored via immunohistochemical staining and western blotting analysis. Results PPRFT displayed lung-protective effects through decreasing oxidative stress, airway inflammation , and lung tissue damage in OVA-induced mice, which was demonstrated by decreasing inflammatory cell levels, IL-6, IL-1β, and TNF-α levels in BALF, and IgE levels in serum, decreasing EPO, NO, and MDA levels in lung tissue, elevating SOD and GSH-Px levels in lung tissue and lung histopathological changes. In addition, PPRFT could regulate the imbalance in Th17/Treg cell ratios, suppress RORγt, and increase the expression of IL-10 and Foxp3 in the lung. Moreover, PPRFT treatment led to decreased expression of IL-6, p-JAK2/Jak2, p-STAT3/STAT3, IL-17, NF-κB, p-AKT/AKT, and p-PI3K/PI3K. Serum metabolomics analysis revealed that 35 metabolites were significantly different among different groups. Pathway enrichment analysis indicated that 31 pathways were involved. Moreover, correlation analysis and metabolic pathway analysis identified three key metabolic pathways: galactose metabolism; tricarboxylic acid cycle; and glycine, serine , and threonine metabolism. Conclusion This research indicated that PPRFT treatment not only attenuates the clinical symptoms of asthma but is also involved in regulating serum metabolism. The anti-asthmatic activity of PPRFT may be associated with the regulatory effects of IL-6/JAK2/STAT3/IL-17 and PI3K/AKT/NF-κB mechanistic pathways.
研究领域:
药理学
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免疫学
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代谢组学
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中医
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Chinese Medicine
·
2025
·Vol. 20
·期 1
·1-18
·
IF 5.7
Wang Xu,Peng Hui-Ming,Zhang Meng-Ru,Li Jing-Jing,Zhao Chuan-Peng,Zhang Ya-Li,Wang Si-Yu,Zhu Si-Ying,Lu Jian-Kang,Yin Hai-Long,Yin Qiang,Fang Jin-Bo
Background Steroid-resistant asthma (SRA) is a form of asthma resistant to corticosteroid therapy, which is characterized by the presence of neutrophil-predominant inflammatory response and neutrophil extracellular traps (NETs) formation. Hyssopus cuspidatus Boriss., a traditional Uyghur medicine, is known for its efficacy in treating inflammatory lung conditions such as asthma. However, the therapeutic impact and underlying mechanisms of Hyssopus cuspidatus Boriss.’s volatile oil (HVO) in SRA have not been fully elucidated. Methods This study established an ovalbumin/lipopolysaccharide (OVA/LPS)-induced SRA mice model to evaluate the therapeutic effect of HVO on SRA. UPLC-QE-Orbitrap-MS was applied to analyze the serum compositions of HVO. Network pharmacology and molecular docking were employed to uncover the complex mechanisms of HVO in treating SRA and predict potential effective compounds in HVO. Furthermore, in vivo studies in SRA mice and in vitro studies using HL-60 cells and bone marrow neutrophils were conducted to validate the mechanism. Results HVO could significantly ameliorate OVA/LPS-induced SRA symptoms, including airway hyperresponsiveness, airway inflammation, mucus overproduction and airway remodeling. 41 prototype compounds, 65 Phase I metabolites and 50 Phase II metabolites were identified in serum-containing HVO. The integration of network pharmacology with experimental validation revealed that HVO can inhibit the formation of NETs by targeting neutrophil elastase, thereby exerting a therapeutic influence on SRA. Meanwhile, molecular docking results showed that 3-methoxy-4-hydroxy mandelonitrile, 1,2,3,4-tetrahydro-1,5,7-trimethyl-naphthalene, cis-calamenene and aristol-1(10)-en-9-yl isovalerate may be the therapeutic compounds of HVO in treating SRA. Conclusion These findings suggest that HVO is a promising therapeutic candidate for neutrophil-dominant SRA by targeting NETs formation.
研究领域:
药理学
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免疫学
·
呼吸病学
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传统医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Xingyu Luo,Xiaolu Chen,Rongying Ma,Zhaoming Fu,Zuwei Liu,Qianhong Su,Huiling Fu,Yong Yang,Wei Xue
Cancer nanovaccines offer a promising strategy for fighting against tumors, however, the engineering of cancer nanovaccines that can be easily fabricated with tanglesome cancer cell-derived antigens and elicit an adequately strong tumor-specific cellular immunity remains challenging. Herein, metal-phenolic networks (MPNs) are used as an antigen delivery platform to prepare the mannose-modified MPNs nanovaccine loaded with ovalbumin (OVA) and the immunoadjuvant CpG oligodeoxynucleotide (MMOC) through the facile self-assembly. When the model antigen OVA is substituted with cancer cell membrane proteins (CCMPs), the nanovaccine is called MMCC. MMOC markedly activates dendritic cells (DCs) via the mannose-mediated endocytosis and efficiently promotes the antigen cross-presentation, thus inspiring a robust antigen-specific CD8 + T cell response as well as immune memory effect in vivo . Consequently, MMOC exhibits admirable therapeutic and preventive results on E.G7-OVA tumors. Moreover, the combination use of MMCC with anti-PD1 significantly inhibits the growth of 4T1 tumors by strengthening the cellular immunity and decreasing the proportion of regulatory T cells (Tregs). The survival rate of 4T1 tumor-bearing mice in the prophylaxis assay is maintained at 100 % by MMCC over 42 days. Altogether, this study affords a universal and effective nanovaccine preparation strategy for cancer immunotherapy and prevention.
研究领域:
癌症免疫学
·
纳米技术
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生物医学工程
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免疫治疗
✓ 已验证
产品关联
DOI
高影响因子
Analytical Methods
·
2018
·Vol. 10
·期 42
·5112-5117
·
IF 2.073
Yanru Qin,Jingfan Xie,Shuting Li,Changqun Cai,Xiaoming Chen,Guanqun Zhong,Chunyan Chen
Glycoproteins have extraordinary significance for the diagnosis of tumors and cancers. However, in untreated complex biological samples, highly selective and sensitive determination of glycoproteins is still a huge challenge. In this study, a boronate affinity surface molecularly imprinted resonance light scattering (RLS) sensor was constructed to detect glycoproteins. In the RLS sensor, 4-vinylbenzeneboronic acid, which was used as a functional monomer for molecularly imprinted polymers (MIPs), is pH sensitive and can reversibly bind to glycoproteins. In addition, 2-(dimethylamino) ethyl methacrylate was also applied as a pH-responsive component to prepare MIPs. The swelling/shrinking properties of the resultant MIPs are beneficial to rapidly remove template glycoproteins from MIPs. Combining the boronate affinity and MIPs, the RLS sensor can specifically recognize target glycoproteins from sample solutions and sensitively detect them. Under optimum conditions, the RLS sensor has a linear response to ovalbumin (OVA) in the range of 0.5–15 nM with a low detection limit of 0.13 nM. The RLS sensor has been successfully utilized for the detection of OVA in real human blood serum, with a good recovery of 94.0–104%. This approach will provide a promising way to detect glycoproteins in clinical diagnostics.
研究领域:
分析化学
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生物传感器
·
临床诊断
✓ 已验证
产品关联
DOI
高影响因子
ChemistryOpen
·
2019
·Vol. 8
·期 7
·915-921
·
IF 2.205
Zhipeng Dong,Qiyan Wang,Ming Huo,Nanxia Zhang,Bingxia Li,Hongmei Li,Yisong Xu,Meng Chen,Hao Hong,Yue Wang
Graphical Perfectly delivered ! Mannose-modified multi-walled carbon nanotubes (Man-MWCNTs) could efficiently deliver a large amount of antigen to bone marrow derived dendritic cells (DCs) through ligand/receptor interactions of mannose, inducing enhanced BMDCs maturation and cytokines secretion. Dendritic cells (DCs) based cancer immunotherapy is largely dependent on adequate antigen delivery and efficient induction of DCs maturation to produce sufficient antigen presentation and ultimately lead to substantial activation of tumor-specific CD8 + T cells. Carbon nanotubes (CNTs) have attracted great attention in biomedicine because of their unique physicochemical properties. In order to effectively deliver tumor antigens to DCs and trigger a strong anti-tumor immune response, herein, a specific DCs target delivery system was assembled by using multi-walled carbon nanotubes modified with mannose which can specifically bind to the mannose receptor on DCs membrane. Ovalbumin (OVA) as a model antigen, could be adsorbed on the surface of mannose modified multi-walled carbon nanotubes (Man-MWCNTs) with a large drug loading content. This nanotube-antigen complex showed low cytotoxicity to DCs and was efficiently engulfed by DCs to induce DCs maturation and cytokine release in vitro, indicating that it could be a potent antigen-adjuvant nanovector of efficient antigen delivery for therapeutic purpose.
研究领域:
纳米技术
·
免疫学
·
癌症研究
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2022
·Vol. 11
·期 1
·263-277
·
IF 7.59
Zexuan Yu,Mengtong Wu,Yingshuang Huang,Yishu Wang,Yijun Chen,Qiulin Long,Ziming Lin,Lingjing Xue,Caoyun Ju,Can Zhang
Dendritic cells (DCs) that can prime antitumor responses show great potential in tumor immunotherapy, whereas the unsatisfactory effect which can be ascribed in part to the high expression of inhibitory cytokines, such as the suppressor of cytokine signaling 1 (SOCS1), restricts their application. Thus, silencing these genes in DCs is essential for DC-based therapy. However, safe and effective delivery of siRNA to DCs still faces challenges. Herein, we designed single-component lipid nanoparticles comprising a solely cationic lipid (OA2) for introducing siRNA into mouse DCs in order to inhibit the immunosuppressive gene and boost the effector responses of DC-based therapy. Compared to other multi-component lipid nanoparticles, single-component lipid nanoparticles are theoretically easy-to-control and detective, which is beneficial for future translation. We showed that the application of OA2 lipid nanoparticles significantly downregulated the expression of SOCS1 in DCs over 50%, compared with the commercial lipofectine2000. Besides, the treatment of OA2 lipid nanoparticles had no influence on the antigen capture of DCs. Thus, we fabricated a SOCS1-downregulated DC vaccine pulsed with Ova antigen and demonstrated that the antigen presentation and pro-inflammatory factor secretion ability of DCs were improved due to the SOCS1 downregulation, leading to an ameliorated immunosuppressive tumor microenvironment and finally exhibiting potent tumor prevention and suppression in B16-Ova tumor-bearing mice. Single-component lipid nanoparticles, which provide an available vector platform for siRNA delivery to primary DCs, appear to be a potent tool to engineer DCs and in turn boost DC-based tumor immunotherapy.
研究领域:
癌症免疫学
·
纳米技术
·
分子生物学
·
免疫治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2022
·Vol. 11
·期 2
·518-532
·
IF 7.59
Siyu Ma,Xiao Liang,Ning Yang,Jie Yang,Jun Zhang,Xiuhua Pan,Yawen Wei,Zengyi Liu,Qi Shen
Until now, treatment of refractory tumors and uncontrolled metastasis by cancer immunotherapy has not yet achieved satisfactory therapeutic results due to the insufficient in vivo immune response. Here, we proposed the construction of a therapeutic cancer nanovaccine Fe@OVA-IR820 with ferroptosis-inducing and photothermal properties for boosting cancer immunotherapy. Fe3+ ions were chelated inside the exogenous antigen ovalbumin (OVA) by biomineralization to form the nanovaccine, to which the photosensitizer IR820 was loaded by electrostatic incorporation. After intratumoral injection, in situ immunogenic cell death (ICD) was triggered as a result of Fe3+-dependent ferroptosis. Endogenous neoantigens and damage-associated molecular patterns (DAMPs) were released because of ICD and worked synergically with the exogenous OVA to provoke the immune response, which was further amplified by the photothermal effect after near-infrared irradiation. The enhanced recruitment and infiltration of T cells were observed and resulted in the suppression of the primary tumor. The therapeutic regiment that combined Fe@OVA-IR820 nanovaccine with cytotoxic T lymphocyte-associated protein 4 (CTLA-4) checkpoint blockade significantly boosted anti-cancer immunity and inhibited the growth of distal simulated metastases. Therefore, we proposed Fe@OVA-IR820 nanovaccine combined checkpoint blockade as a potential therapeutic strategy for melanoma treatment.
研究领域:
癌症研究
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纳米技术
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免疫治疗
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生物医学工程
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药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
·
2023
·
IF 6
Yuan Gao,Yingxi Zhang,Hong Xia,Yuqing Ren,Haibin Zhang,Siwen Huang,Meiju Li,Yongjun Wang,Heran Li,Hongzhuo Liu
Nanocarrier antigen-drug delivery system interacts specifically with immune cells and provides intelligent delivery modes to improve antigen delivery efficiency and facilitate immune progression. However, these nanoparticles often have weak adhesion to cells, followed by insufficient cell absorption, leading to a failed immune response. Inspired by the structure and function of viruses, virus-like mesoporous silica nanoparticles (VMSNs) were prepared by simulating the surface structure, centripetal-radialized spike structure and rough surface topology of the virus and co-acted with the toll-like receptor 7/8 agonist imiquimod (IMQ) and antigens oocyte albumin (OVA). Compared to the conventional spherical mesoporous silica nanoparticles (MSNs), VMSNs which was proven to be biocompatible in both cellular and in vivo level, had higher cell invasion ability and unique endocytosis pathway that was released from lysosomes and promoted antigen cross-expression. Furthermore, VMSNs effectively inhibited B16-OVA tumor growth by activating DCs maturation and increasing the proportion of CD8+ T cells. This work demonstrated that virus-like mesoporous silica nanoparticles co-supply OVA and IMQ, could induce potent tumor immune responses and inhibit tumor growth as a consequence of the surface spike structure induces a robust cellular immune response, and undoubtedly provided a good basis for further optimizing the nanovaccine delivery system.
研究领域:
纳米技术
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生物医学工程
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免疫学
·
癌症研究
·
药学
✓ 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）