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ACS Applied Materials & Interfaces · 2020 · IF 8.758

Lentinan-Functionalized Graphene Oxide Is an Effective Antigen Delivery System That Modulates Innate Immunity and Improves Adaptive Immunity

Zhenguang Liu,Jin He,Tianyu Zhu,Cong Hu,Ruonan Bo,Adelijiang Wusiman,Yuanliang Hu,Deyun Wang

Graphene oxide (GO) and lentinan have received great attention because of their utility in biomedical applications. Graphene oxide is utilized in drug- and vaccine-delivery systems due to its biocompatibility, large surface area, and outstanding adsorption capability, while lentinan has immunity-enhancing effects. In this study, we synthesized and characterized GO grafted with lentinan (LNT) as an adjuvant and investigated how to impact the immune responses. Lentinan-modified GO (GO-LNT) facilitated antigen uptake in macrophages and improved the efficiency of antigen application in vitro. Furthermore, in vivo, compared with GO/OVA, GO-LNT/OVA decreased the release rate of ovalbumin (OVA) to sustain long-term immune responses and boost the levels of IgG and IgG subtypes. Hence, we can infer that the effects of GO-LNT were a result of the increased amounts of antigen uptake by cells. Overall, our studies demonstrated that GO-LNT could suffice for a safe and effective vaccine-delivery system as well as an excellent adjuvant that both elicits a long-term immune memory response and potentiates cellular and humoral immunity.

CAS / MDL: 34819-78-8
研究领域: 生物医学工程 · 免疫学 · 药剂学
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OPTICS AND LASER TECHNOLOGY · 2018 · IF 2.503

Sensitivity enhanced SPR immunosensor based on graphene oxide and SPA co-modified photonic crystal fiber

Qi Wang,Botao Wang

A sensitivity enhanced surface plasmon resonance (SPR) immunosensor based on Graphene oxide (GO) composite and staphylococcal protein A (SPA) co-modified photonic crystal fiber (PCF) is developed for human IgG detection. The PCF spliced between two section of multimode fibers (MMFs) is sputtered with gold film, which was then modified with graphene oxide and SPA for further immunosensing. Graphene oxide with abundant functional groups has a large surface area for more biomolecules immobilization and can enhance the interaction between Au film and external medium, leading to the sensitivity increased greatly. SPA can specifically bind the Fc region of the antibodies and has a high degree of orientation for capturing antibodies. Experimental results indicated that the refractive index (RI) sensitivity of graphene oxide modified Au-PCF SPR sensor reaches 4649.8 nm/RIU, which is about 1888 nm/RIU higher than that without graphene oxide film and the human IgG detection limit reaches as low as 10 ng/mL. Such a sensitivity enhanced immunosensor based on graphene oxide and SPA co-modified PCF shows a great promise in biosensing.

研究领域: 生物传感 · 免疫学
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SENSORS AND ACTUATORS B-CHEMICAL · 2017 · IF 5.401

Reduced graphene oxide-based optical sensor for detecting specific protein

Wen-Shuai Jiang,Wei Xin,Shuang Xun,Shao-Nan Chen,Xiao-Guang Gao,Zhi-Bo Liu,Jian-Guo Tian

A sensitive and selective optical biosensor based on reduced graphene oxide (RGO), which uses the polarization-dependent absorption effect of graphene under total internal reflection, is reported for determination of rabbit IgG. RGO sheets with the thickness of about 8.1   nm are fabricated by high temperature reduction and used as a sensing film, because of its strong polarization dependent absorption. This RGO-based optical sensor shows a satisfactory response to rabbit IgG with a minimum concentration of 0.0625   μg/ml. As a contrast, commercial SPR apparatus is used to investigate rabbit IgG with a minimum concentration of 0.3125   μg/ml. Moreover, with antigen–antibody binding, this sensor can also achieve label-free and real-time detection. Taking into account these factors, the RGO-based optical sensor may be a potential candidate for biosensing.

CAS / MDL: 25952-53-8 6066-82-6
研究领域: 材料科学 · 生物传感器 · 光学
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JOURNAL OF BIOMEDICAL OPTICS · 2017 · IF 2.53

Optical demodulation system for digitally encoded suspension array in fluoroimmunoassay

Qinghua He,Dongmei Li,Yonghong He,Tian Guan,Yilong Zhang,Zhiyuan Shen,Xuejing Chen,Siyu Liu,Bangrong Lu,Yanhong Ji

A laser-induced breakdown spectroscopy and fluorescence spectroscopy-coupled optical system is reported to demodulate digitally encoded suspension array in fluoroimmunoassay. It takes advantage of the plasma emissions of assembled elemental materials to digitally decode the suspension array, providing a more stable and accurate recognition to target biomolecules. By separating the decoding procedure of suspension array and adsorption quantity calculation of biomolecules into two independent channels, the cross talk between decoding and label signals in traditional methods had been successfully avoided, which promoted the accuracy of both processes and realized more sensitive quantitative detection of target biomolecules. We carried a multiplexed detection of several types of anti-IgG to verify the quantitative analysis performance of the system. A limit of detection of 1.48×10−10  M was achieved, demonstrating the detection sensitivity of the optical demodulation system.

研究领域: 生物医学工程 · 分析化学 · 免疫学
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SENSORS AND ACTUATORS B-CHEMICAL · 2022 · IF 9.221

Ultrasensitive total internal reflection sensor with rotatory biased weak measurement

Chongqi Zhou,Yang Xu,Xiaonan Zhang,Zhangyan Li,Tian Guan,Yonghong He,Yanhong Ji

A modified weak measurement scheme, rotatory biased weak measurement, is proposed to significantly improve the sensitivity and resolution of the total internal reflection sensor. This method introduces an additional phase in the post-selected procedure and generates an extinction point in the spectrum distribution. The biased post-selection makes smaller coupling strength available, which leads to an enhancement of phase sensitivity and refractive index sensitivity. In rotatory biased weak measurement, an enhanced refractive index sensitivity of 13605 nm/RIU is achieved compared to 1644 nm/RIU in standard weak measurement. The performance of total internal reflection sensors with different sensitivity is analyzed, and it is shown the optimal refractive index resolution of sensors increases with sensitivity. An optimal refractive index resolution of 4 × 1 0 − 7 RIU on a total reflection structure is demonstrated, which is far beyond the state-of-the-art resolution of 3 × 1 0 − 6 RIU of total internal reflection sensors. The rabbit anti-mouse IgG and mouse IgG binding reaction experiments demonstrate that our system has a high response to the concentration of IgG in a wide range and the limit of detection is 15 ng/mL. This work provides a total internal reflection sensor with the advantages of simple structure, low cost, and high resolution at the same time.

研究领域: 光学 · 传感器 · 生物物理学
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JOURNAL OF PEPTIDE SCIENCE · 2022 ·Vol. 28 ·期 10 ·e3411 · IF 2.408

Characterization of a heptapeptide-modified microsphere for oriented antibody immobilization

Shu Bai,Jie Zhang,Liyan Zhu,Xiaoxing Gong,Linling Yu,Yan Sun

Oriented immobilization of antibodies is important for the effective recognition of target antigens. In this paper, a heptapeptide ligand, HWRGWVC (HC7), was modified onto non-porous monosized poly(glyceryl methacrylate) (pGMA) microspheres (named pGMA-HC7) to explore the antibody immobilization behaviors. Characterization of the microspheres by particle size analyzer, scanning electron microscopy, Fourier transform infrared spectroscopy, and reversed-phase chromatography proved the success of each fabrication step. The capacity and activity of antibody immobilization through HC7 were studied using immunoglobulin G (IgG) as a model antibody and horseradish peroxidase (HRP) as a model antigen. Additionally, IgG immobilizations on pGMA microspheres by nonspecific adsorption and covalent coupling through carbodiimide chemistry were conducted for comparison. pGMA-HC7 exhibited an IgG adsorption capacity of 3–4 mg/g in 10 min by the specific binding of HC7 without nonspecific interactions. Notably, the ligand HC7 showed a by two orders of magnitude stronger affinity for IgG than its original hexapeptide ligand HWRGWV. Moreover, the capacity and activity of the immobilized anti-HRP antibody on pGMA-HC7 were 1.6-fold and 3-fold higher than those of the covalent coupling, respectively. The results proved the superior role of HWRGWVC in the affinity binding of antibody and the potential of pGMA-HC7-25 in immunoassay and immunodiagnostic applications.

CAS / MDL: 78-67-1
研究领域: 生物化学 · 生物技术 · 材料科学 · 免疫学
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VACCINE · 2022 · IF 4.169

Chitosan-functionalized graphene oxide as adjuvant in HEV P239 vaccine

Qianyu Bai,Zhiwen Wang,Yina AN,Jijing Tian,Zhilin Li,Yifei Yang,Yanjun Dong,Mingyong Chen,Tianlong Liu

Searching appropriate adjuvants for vaccine is a potent method to intense the immune efficacy. In the present study, we developed a novel Hepatitis E virus (HEV) vaccine by utilizing chitosan modified nano-graphene oxide (GO-CS) as an adjuvant to support HEV antigen P239 protein (GO/CS/P239). The characterization of GO/CS/P239 was observed by atomic force microscope. The safety of GO/CS/P239 was measured by CCK-8 method, hemolysis test and acute challenge test. The anti-HEV titers and cytokines production were analyzed by double antibody sandwich ELISA . As the results showed, by contrast with a vaccine that contained only the P239 protein, GO/CS/P239 vaccine can promote immune cells to produce more IgG antibodies and cytokines, which were able to stimulate the organism to produce stronger both cellular and humoral immunity. Collectively, GO/CS/P239 particles have been demonstrated to be safe both in vitro and in vivo, and can facilitate sufficient immune response to protect organisms from virus infection , which suggested that our exploration offers a promising alternative vaccine that can control HEV infection.

CAS / MDL: 75-15-0
研究领域: 免疫学 · 病毒学 · 纳米技术 · 药学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2020 · IF 5.162

Adjuvant activities of CTAB-modified Polygonatum sibiricum polysaccharide cubosomes on immune responses to ovalbumin in mice

Zhenguang Liu,Haiyu Ni,Lin Yu,Shuwen Xu,Ruonan Bo,Tianxin Qiu,Pengfei Gu,TianYu Zhu,Jin He,Adelijiang Wusiman,Shaowu Zhu,Jiaguo Liu,Yuanliang Hu,Deyun Wang

Recently, the cubosomes have been widely studied as drug carriers. It has been described that cubosomes could further stimulate the immune response after carrying the immune enhancer. Polygonatum sibiricum polysaccharide (PSP), one of the most important biologically active ingredients of Polygonatum sibiricum , has been reported as an immunostimulant to improve immune responses. This study was aimed to observe the immunomodulation effects of ovalbumin (OVA) absorbed cetyltrimethylammonium bromide-modified Polygonatum sibiricum polysaccharide cubosomes (CTAB-modified PSP-Cubs/OVA). Firstly, the antigen uptake of CTAB-modified PSP-Cubs/OVA by macrophages was determined in vitro. After that, mice were immunized with CTAB-modified PSP-Cubs/OVA. The activation of dendritic cells in lymph nodes, activation of lymphocyte, ratios of CD4 + to CD8 + , the concentrations of OVA-specific IgG in serum and the cytokines concentrations were analyzed. As the results showed, CTAB-modified PSP-Cubs/OVA could promote the production of OVA-specific IgG in serum. The ratio of CD4 + to CD8 + in CTAB-modified PSP-Cubs/OVA group was significantly increased compared with other groups. CTAB-modified PSP-Cubs/OVA could significantly activate dendritic cells and promote lymphocyte proliferation. The results indicated that CTAB-modified PSP-Cubs/OVA could promote the secretion of related cytokines and the proliferation of lymphocytes, stimulate the cellular immune response and increase the level of humoral immunity. Above all, CTAB-modified PSP-Cubs had good adjuvant activity.

CAS / MDL: 57-09-0
研究领域: 免疫学 · 药剂学 · 生物技术
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Frontiers in Chemistry · 2024 · IF 3.8

An ultra-sensitive biosensor based on surface plasmon resonance and weak value amplification

Zhang Lizhong,He Mingyi,Xu Yang,Guo Cuixia,Zhou Chongqi,Guan Tian

An ultra-sensitive phase plasmonic sensor combined with weak value amplification is proposed for the detection of IgG, as a model analyte. Phase detection is accomplished by self-interference between the p-polarization and the s-polarization of the light. With the principles of weak value amplification, a phase compensator is used to modulate the coupling strength and enhance the refractive index sensitivity of the system. On a simple Au-coated prism-coupled surface plasmon resonance (SPR) structure, the scheme, called WMSPR, achieves a refractive index sensitivity of 4.737 × 104 nm/RIU, which is about three times higher than that of the conventional phase-based approach. The proposed WMSPR biosensor gives great characteristics with a high resolution of 6.333 × 10−8 RIU and a low limit of detection (LOD) of 5.3 ng/mL. The results yield a great scope to promote the optimization of other SPR biosensors for high sensitivity.

CAS / MDL: 77-86-1 51-61-6
研究领域: 光学 · 生物传感 · 纳米技术 · 分析化学
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2024 · IF 7.7

Immune enhancement of rhamnolipid/manganese calcium phosphate mineralized nanoparticle: A promising subunit antigen delivery system

Zheng Jia,Xinyao Zhou,Jingjing Liu,Xinqi De,Yifan Li,Zaixing Yang,Haoyuan Duan,Fang Wang,Junwei Ge

The use of biomimetic mineralization strategy is promising to solve the problem of poor stability and immune effect of subunit antigens. However, non-specifically inducing protein mineralization is still a challenge. we hypothesized that rhamnolipids with both protein and metal binding capacity could be used to develop more functional and biocompatible calcium mineralized nanoparticle (RMCP). The results show that rhamnolipids synergistically enhanced the mineralization of protein with manganese ions and improved 21 % the loading antigens of RMCP compared to manganese calcium phosphate nanoparticles. Transmission electron microscopy (TEM) and Dynamic Light Scattering (DLS) showed particle size of RMCP is 260 ± 12.1 nm with spherical morphology. In vitro experiments have shown that RMCP effectively activate immune cells through the cGAS-STING and NLRP3 pathways and demonstrated a higher level of cytokines in RAW264.7 Macrophages. In vivo, RMCP triggered an increased IgG titer with 16.5-fold IgG2a/IgG1 ratio compared to the aluminum adjuvant which improved the recovery status after challenge in mice. We used biological surfactants for the first time to enhance the biomimetic mineralization process of subunit antigen, which provides a new approach for constructing calcium-based biocompatible antigen delivery vectors, helping to develop a new generation of stable, efficient, and safe subunit vaccines.

CAS / MDL: 10043-52-4 7785-87-7
研究领域: 免疫学 · 纳米技术 · 疫苗开发 · 生物材料
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SENSORS AND ACTUATORS B-CHEMICAL · 2018 · IF 5.667

Colorimetric/chemiluminescent immunochromatographic test strip by using luminol-reduced gold nanoparticles as dual-response probes

Hui Ouyang,Mengyao Wang,Wenwen Wang,Zhifeng Fu

Luminol-reduced gold nanoparticles (LuReGNPs) were prepared and utilized as dual-response signal probes for the development of a colorimetric/chemiluminescent immunochromatographic test strip (ITS). LuReGNPs-labeled antibody was adopted as the signal tracer to conduct immunoassay of mouse IgG using the developed ITS device. After 6-min competitive immunoreaction, the tracer antibody was captured on the test zone, which led to accumulation of LuReGNPs. The appearance of red color resulting from LuReGNPs accumulation on the test zone was observed by naked eyes as a qualitative and semi-quantitative signal. Moreover, luminophore in the signal probes enabled sensitive quantitation after initiating the luminol-H 2 O 2 chemiluminescent reaction. Under the optimal conditions, mouse IgG was detected within a linear range of 0.10–100 ng/mL with a detection limit of 0.033 ng/mL (S/N = 3). The results for real biological samples detection and recovery tests demonstrated the acceptable reliability of the dual-response ITS. It exhibited great potential in both rapid screening and sensitive quantitation. Due to the merits of facile manipulation, short detection time and ideal portability, the platform could be further extended to multianalyte immunoassay of biomarker proteins for point-of-care test.

CAS / MDL: 16961-25-4
研究领域: 分析化学 · 纳米技术 · 生物医学工程 · 即时检测
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SENSORS AND ACTUATORS B-CHEMICAL · 2014 · IF 3.84

A novel disposable immunosensor based on quenching of electrochemiluminescence emission of Ru(bpy)32+ by amorphous carbon nanoparticles

He Zhou,Huan Yue,Yali Zhou,Lin Wang,Zhifeng Fu

Novel amorphous carbon nanoparticles (ACNPs) with high electrochemiluminescence (ECL) quenching efficiency were prepared from candle soot with a quite simple approach. The prepared ACNPs were employed as novel energy quenchers for an ECL immunosensor on a disposable screen-printed carbon electrode array (SPCEA) substrate. Gold nanoparticles-doped chitosan composite film was utilized to immobilize Ru(bpy) 3 2+ -labeled antibody on the SPCEA, and ACNPs were linked with antigens to obtain ACNP-antigen conjugate. The immunoreaction between the Ru(bpy) 3 2+ -labeled antibody and the ACNP-antigen conjugate bridged the Ru(bpy) 3 2+ donor and the ACNPs acceptor, which led to quenching of ECL emission from Ru(bpy) 3 2+ via energy transfer. In the presence of the target antigen, this antigen competed with the ACNP-antigen for the immobilized Ru(bpy) 3 2+ -labeled antibody, thus led to decreased occurrence of the ECL quenching. This ACNPs-based ECL quenching system was successfully applied to detect mouse IgG, which was used as a model analyte. The method showed a linear range of 0.50–400   ng   mL −1 and a detection limit of 0.35   ng   mL −1 . The results for real sample assay and recovery test demonstrated the reliability of this ECL quenching-based immunosensor. It could be further extended to multiplexed immunoassay of biomarker proteins for clinical diagnosis.

研究领域: 分析化学 · 生物传感器 · 纳米技术 · 临床诊断
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