Nature Nanotechnology
·
2023
·
IF 38.3
Zuo Yanming,Ye Jingjia,Cai Wanxiong,Guo Binjie,Chen Xiangfeng,Lin Lingmin,Jin Shuang,Zheng Hanyu,Fang Ao,Qian Xingran,Abdelrahman Zeinab,Wang Zhiping,Zhang Zhipeng,Chen Zuobin,Yu Bin,Gu Xiaosong,Wang Xuhua
Despite considerable unmet medical needs, effective pharmacological treatments that promote functional recovery after spinal cord injury remain limited. Although multiple pathological events are implicated in spinal cord injuries, the development of a microinvasive pharmacological approach that simultaneously targets the different mechanisms involved in spinal cord injury remains a formidable challenge. Here we report the development of a microinvasive nanodrug delivery system that consists of amphiphilic copolymers responsive to reactive oxygen species and an encapsulated neurotransmitter-conjugated KCC2 agonist. Upon intravenous administration, the nanodrugs enter the injured spinal cord due to a disruption in the blood–spinal cord barrier and disassembly due to damage-triggered reactive oxygen species. The nanodrugs exhibit dual functions in the injured spinal cord: scavenging accumulated reactive oxygen species in the lesion, thereby protecting spared tissues, and facilitating the integration of spared circuits into the host spinal cord through targeted modulation of inhibitory neurons. This microinvasive treatment leads to notable functional recovery in rats with contusive spinal cord injury.
研究领域:
神经科学
·
药理学
·
纳米技术
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产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2023
·
IF 19
Jun-Jun Wu,Guan-Jie Chen,Chen-Yuan Fan,Fan Shen,Yi Yang,Wei Pang,Zhen-Nan Zhao,Hong-Xin Guan,Huan Wu,Ying Lu,Ya-Juan Fu,Qi Chen,Yong-Tang Zheng,Songying Ouyang
The pandemics induced by emerging SARS-CoV-2 variants and monkeypox virus infection have triggered the urgent need for broad-spectrum vaccines. Except for “super” antigen designs, pattern recognition receptor (PRR) agonist-based adjuvants might blaze a new trail, through enhancing the immune response of conserved antigen epitopes shared among variants for cross-protection. Ideal adjuvants with proper adjustments could be conveniently applied to different antigens and antigen types in response to new pandemics. However, general strategies for modulating PRR agonist-based adjuvant properties to tailor the optimal immunity remain to be further explored. Here, an adjuvant platform STINGsome is described, composed of a STING agonist and pH-switchable IP9 liposomes, to simulate viral infection via STING activation and necroptosis. STINGsomes function as an efficient adjuvant to elicit broad and potent immune responses against multiple SARS-CoV-2 VOCs (Omicron BA.1, BA.2, BA.3, BA.4/5) and a monkeypox virus. More importantly, the adjuvant properties of STINGsomes can be tuned by simply adjusting the IP9 percentage, owing to distinct kinetics from local release to lymph node stimulation. Thus, this study provides a relatively simple strategy to adapt an adjuvant platform to different pathogenic antigens, ultimately achieving optimal protective responses.
研究领域:
免疫学
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病毒学
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药学
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生物技术
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产品关联
DOI
高影响因子
DYES AND PIGMENTS
·
2023
·
IF 4.5
Meng-Nan Li,Jing-Yu Zhao,Gang Zhang,Yu-Jie Xu,Jian-Feng Ge,Ru Sun
In this paper, several novel nitrogen-containing heterocycle dyes 1a-c with large conjugated planar structures based on naphthyridine derivatives were designed and synthesized, which had excellent optical properties and biological applications. Optical test showed the maximum absorption wavelengths of 1a-c were in the range of 443–485 nm, while the maximum emission wavelengths located at 523–610 nm in difference solvents. Furthermore, they exhibited polarity related fluorescence intensity changes with high fluorescence quantum yields, even up to 88% ( 1a in THF). Moreover, the transient absorption spectra revealed the excited-state lifetime of dye 1a became shorter with the increase of solvent polarity. Density functional theory calculations are also used to help explain the effect of the polarity of solvents on their fluorescence properties. Interestingly, the dyes 1a-c were somewhat toxic to cancer cells, while had an obvious growth-promoting effect on normal cells. Additionally, 1a-c with excellent lipid droplet (LD) targeting could be used for long-term observation of targeted cellular lis) hysiological activity and further applied to dynamic monitoring of changes in LDs polarity stimulated by TLR4 activator (LPS) in living cells. Overall, the excellent optical properties and biocompatibility of 1a-c indicate that they can serve as fluorescent probes for biological applications, and the results have important implications for understanding the physiological functions of LDs, especially in terms of morphological and polar changes.
研究领域:
生物化学
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细胞生物学
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分子生物学
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DOI
高影响因子
ELECTROPHORESIS
·
2012
·Vol. 34
·期 2
·277-283
·
IF 3.303
Libo Li,Hongwei Du,Huan Yu,Lei Xu,Tianyan You
CE coupled with amperometric detection method was developed using ionic liquid 1-ethyl-3-methylimidazolium tetrafluoroborate (EMImBF 4 ) as additive for the simultaneous detection of clenbuterol (CLB), terbutaline (TER), and ractopamine (RAC) in feed. The effects of detection potential, concentration of EMImBF 4 , pH, and concentration of the running buffer, separation voltage as well as injection time on the separation and detection of these three β -agonists were investigated in detail. Under the optimum conditions: the detection potential at 1.05 V, 50 mmol/L Tris-HAc at pH 8.0 with 0.6% (v/v) EMImBF 4 , electrokinetic injection 6 s at 16 kV and separation voltage at 16 kV, a baseline separation for these three analytes could be achieved within 11 min. Introduction of EMImBF 4 into the running buffer resulted in significant improvement in separation selectivity and enhancement in peak currents for those β -agonists, especially for TER and RAC, which could not be separated in the running buffer without additive. The method exhibited wide linear range with LOD (S/N = 3) of 2, 1, and 2 nmol/L for CLB, TER, and RAC, respectively. The precision was determined in both intraday ( n = 5) and interday ( n = 3) assays, and the RSDs for both migration time and peak current were less than 6%. The proposed method was also applied to analyze β -agonists in feed sample.
研究领域:
分析化学
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兽医药理学
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2025
·
IF 12.9
Zhanxue Xu,Xinrui Yang,Xingyu Lu,Dandan Su,Yidan Wang,Huixing Wu,Zhenhua Zhang,Changrui Long,Liqian Su,Yanyu Wang,Hongbo Chen,Shijian Xiang,Benjie Zhou
Combination therapies for melanoma face challenges due to asynchronous drug delivery and associated toxicity, underscoring the need for advanced delivery systems. While immune checkpoint inhibitors (ICIs) enhance T cell activity, optimal cytotoxic responses require efficient antigen presentation by mature dendritic cells (DCs), which are often functionally impaired in the tumor microenvironment. Thus, effective treatment requires coordinated T cell activation, DC-mediated priming, and direct tumor suppression. Herein, wild Glycyrrhiza uralensis Fisch roots-derived nanovesicles (GC NV) are demonstrated to be effective inhibitors of melanoma proliferation. The vesicles exert this activity through the intracellular delivery of encapsulated miRNA (miR2916) and bioactive molecules (isoliquiritigenin), with this capacity for intracellular delivery extending to the STING agonist DMXAA. We also demonstrate how chemical modification can be used to install PD-L1 antibodies on the membrane surface of these GC NV, imbuing these vesicles with selectivity for tumor cells. Combining DMXAA encapsulation with surface-displayed PD-L1 antibodies creates vesicles (GP@DMX NV) that both promote DCs maturation and elicit CD8 + T cell response. Our multifunctional GP@DMX NV reverse the immunosuppressive microenvironment of melanoma and significantly enhance the immunotherapeutic potential of immune checkpoints.
研究领域:
肿瘤学
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药剂学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Nano
·
2025
·
IF 16
Yan Deng,Hao Cheng,Ji Zhu,Yue Jiang,Hongwu Sun,Guocheng Li,Jing Wei,Ruoyi Xue,Rang Feng,Jingwen Cao,Wenkang Yu,Yalan Wang,Mingqi Xu,Quanming Zou,Haibo Li
Parenteral subunit vaccines typically elicit systemic humoral immune responses but often struggle to induce mucosal immunity. Herein, we developed a promising adjuvant system, TB/P2C-NE, a tamibarotene-loaded nanoemulsion incorporating the TLR2/6 agonist Pam2CSK4. Upon intramuscular vaccination, TB/P2C-NE promoted antigen-specific mucosal immune responses in the gastrointestinal tract, accompanied by systemic humoral and cellular response. Mechanistically, tamibarotene upregulated the intestinal homing molecule CCR9 on lymphocytes through dendritic cell modulation, while Pam2CSK4 increased IL-6 secretion at the injection sites, further amplifying CCR9 expression and lymphocyte activation and leading to enhanced lymphocyte homing to the intestinal mucosa and a subsequent boost in mucosal immunity. Notably, TB/P2C-NE induced long-term gastrointestinal mucosal responses, maintaining elevated sIgA levels for up to three months post-immunization, and also induced gastrointestinal mucosal immunity in combination with a polysaccharide conjugate antigen. Immunization with recombinant intimin using TB/P2C-NE as the adjuvant resulted in a robust protective effect against the EHEC O157:H7 challenge. In summary, TB/P2C-NE offers an adjuvant strategy potentially accelerating the development of vaccines targeting gastrointestinal infections.
研究领域:
免疫学
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疫苗学
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药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Analytical Methods
·
2014
·Vol. 6
·期 24
·9684-9690
·
IF 1.938
Xu Chen,Yong Luo,Bo Shi,Xianming Liu,Zhigang Gao,Yuguang Du,Weijie Zhao,Bingcheng Lin
β-Agonists are a group of illegal but widely used feed additives in the stockbreeding industry. In order to achieve simple-to-use, fast and high-throughput testing of this banned chemical, herein we suggest a paper-based analytical device on which a chemiluminescence diminishment method was performed. In this approach, extracts from swine hair samples as well as luminescent reagents, such as luminol and potassium periodate solution, in a low volume were applied to our device. It was found that the light emission was diminished by the β-agonists extracted from the swine hair samples. The degree of diminishment is proportional to the concentration of the β-agonists from 1.0 × 10−5 to 1.0 × 10−8 mol L−1. Also, the concentrations of solutions for chemiluminescence were optimized. The mechanism and reaction kinetics of chemiluminescence were discussed as well. The detection limit was obtained as 1.0 × 10−9 mol L−1, and recoveries from 96% to 110% were achieved, both of which suggested that our method will be favourable in field applications for swine hair samples.
研究领域:
分析化学
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兽医学
·
食品安全
✓ 已验证
产品关联
DOI
高影响因子
BIOMATERIALS
·
2023
·
IF 14
Bo Chen,Ruijie Huang,Wei Zeng,Wei Wang,Yuanzeng Min
The immunosuppressive tumor microenvironment (TME) greatly limits the actual outcome of immunotherapy. Therefore, it is urgent to develop appropriate strategies to reshape the TME and ultimately induce a strong immune response. Here, we developed a dual-functional liposome loaded with the photothermal agent IR808 near the infrared region (NIR) and Toll-like-receptor-7 (TLR7) agonist loxoribine prodrug (Lipo@IR808@Loxo) to achieve NIR light-triggered photothermal therapy (PTT) and the targeted delivery of immune adjuvants. Under NIR irradiation, Lipo@IR808@Loxo could greatly improve the efficiency of PTT to directly kill tumor cells and release tumor-associated antigens, which could work together with loaded loxoribine to relieve the immunosuppressive TME, effectively promoting the activation of antigen-presenting cells and subsequent antigen presentation . In this way, Lipo@IR808@Loxo could act as an in situ therapeutic cancer vaccine, eventually inducing a potent antitumor T-cell response. When further combined with immune checkpoint blockade, Lipo@IR808@Loxo-mediated photothermal immunotherapy could not only eliminate the primary tumors but also inhibit the growth of distant tumors, thus enhancing the abscopal effect.
研究领域:
肿瘤学
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免疫学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Ying Xu,Jing Yang,Xiongyan Meng,Shuai Meng,Tiantian Sun,Ning Ding,Chengli Zong
Covalently linking an adjuvant to an antigenic protein enhances its immunogenicity by ensuring a synergistic delivery to the immune system, fostering a more robust and targeted immune response. Most adjuvant-protein conjugate vaccines incorporate only one adjuvant due to the difficulties in its synthesis. However, there is a growing interest in developing vaccines with multiple adjuvants designed to elicit a more robust and targeted immune response by engaging different aspects of the immune system for complex diseases where traditional vaccines fall short. Here, we pioneer the synthesis of a dual-adjuvants protein conjugate Vaccine 1 by assembling a toll-like receptor 7/8 (TLR7/8) agonist, an invariant natural killer T cell (iNKT) agonist with a clickable bicyclononyne (BCN). The BCN group can bio-orthogonally react with azide-modified severe acute respiratory syndrome coronavirus-2 receptor-binding domain (SARS-CoV-2 RBD) trimer antigen to give the three-component Vaccine 1 . Notably, with a mere 3 μg antigen, it elicited a balanced subclass of IgG titers and 20-fold more IgG2a than control vaccines, highlighting its potential for enhancing antibody-dependent cellular cytotoxicity. This strategy provides a practicable way to synthesize covalently linked dual immunostimulants. It expands the fully synthetic self-adjuvant protein vaccine that uses a single adjuvant to include two different types of adjuvants.
研究领域:
免疫学
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病毒学
·
药物化学
·
疫苗研发
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DOI
高影响因子
ACS Nano
·
2025
·
IF 16
Xiaotong Chen,Lei Lei,Jiayao Yan,Xingzhou Wang,Lin Li,Qin Liu,Ying Wang,Tianran Chen,Jie Shao,Lixia Yu,Zijian Li,Lijing Zhu,Lifeng Wang,Baorui Liu
Although personalized neoantigen cancer vaccines have emerged as a promising strategy for cancer treatment, challenges remain to develop immune-stimulatory carriers which allow simultaneous transport of adjuvants and vaccines to lymph nodes (LNs). With inherent immunogenicity, genetic plasticity, and efficiency for large-scale production, M13 phages represent an attractive platform for vaccine delivery as natural bionanomaterials. Here, we report the discovery of an anti-CD40 designed ankyrin repeat protein (DARPin) and propose a bifunctional M13 ph age for neoantigen delivery based on this anti-CD40 DARPin protein (M13CD40). M13CD40-based neoantigen vaccines show improved accumulation and prolonged antigen retention in LNs compared with nontargeting phage vaccines due to the abundance of CD40-positive cells in LNs. Besides the intrinsic immunogenicity of phages, M13CD40-based neoantigen vaccines also benefit from additional CD40 stimulation due to multiple copies of anti-CD40 DARPins displayed on M13CD40 phages. Subcutaneous immunization with M13CD40-based neoantigen vaccines results in more robust antigen-specific immune responses and superior antitumor efficacy in poorly immunogenic tumor models compared with nontargeting phage vaccines. Combination therapy with PD-1 blockade further enhances T cell cytotoxicity and improves tumor control. To summarize, our findings highlight M13CD40 as a CD40 nanoagonist as well as an efficient vehicle for LN-targeted delivery of personalized neoantigen vaccines.
研究领域:
肿瘤学
·
免疫学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF COLLOID AND INTERFACE SCIENCE
·
2025
·
IF 9.7
Qingdong Li,Yuanyuan Cui,Zhenhong Xia,Wenjuan Gao,Jianmin Xiao,Zhen Zhao,Lei Yang,Guilong Zhang,Zhengyan Wu
Immunotherapy has emerged as a promising approach for melanoma treatment. However, the efficacy of traditional immune checkpoint inhibitors (ICIs) remains limited due to the immunosuppressive tumor microenvironment. In this study, a novel nano-immune agonist, pLCGM-OVA, was developed to induce cuproptosis and activate the cGAS-STING pathway, thereby enhancing melanoma immunotherapy. The pLCGM-OVA was synthesized by conjugating PDGFB with liposomes that encapsulate CuGdMn nanoclusters (CGM) and ovalbumin (OVA). Upon exposure to the acidic microenvironment of tumours, pLCGM-OVA undergoes degradation, releasing Cu ions, Mn ions, and free OVA. This release triggers reactive oxygen species-mediated cuproptosis and activates the cGAS-STING pathway via Mn, leading to the subsequent induction of immunogenic cell death (ICD). Simultaneously, free OVA and ICD antigens are presented to dendritic cells (DCs), promoting their maturation and enhancing cytotoxic T lymphocyte infiltration, thus improving the efficacy of tumour immunotherapy. In vitro and in vivo studies demonstrated that pLCGM-OVA significantly inhibited tumour growth and recurrence with minimal systemic toxicity, owing to the combined effects of cuproptosis and immunotherapy. Moreover, pLCGM-OVA exhibited excellent T 1 contrast (9.26 mM −1 s −1 ), significantly enhancing T 1 -weighted magnetic resonance imaging signals of tumours, facilitating accurate melanoma diagnosis. Overall, this work presents a highly promising candidate for the development of potent immune agonists for melanoma treatment.
研究领域:
肿瘤学
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免疫学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOORGANIC & MEDICINAL CHEMISTRY
·
2023
·
IF 3.5
Lu Liu,Zhendong Song,Guangjin Fan,Linlin Lou,Yuanxiang Wang,Xiaolei Zhang,Xiao-Feng Xiong
KRAS serves as a vital regulator for cellular signaling and drives tumor pathogenesis after mutation. Despite extensive research efforts spanning several decades, targeting KRAS is still challenging due to the multiple KRAS mutations and the emergence of drug resistance. Interfering the interactions between KRAS and SOS1 is one of the promising approaches for modulating KRAS functions. Herein, we discovered small-molecule SOS1 agonists with novel indazole scaffold. Through structure-based optimization, compound 11 was identified with high SOS1 activation potency (p-ERK EC 50 = 1.53 μM). In HeLa cells, compound 11 enhances cellular RAS-GTP levels and exhibits biphasic modulation of ERK1/2 phosphorylation through an on-target mechanism and presents the therapeutic potential to modulate RAS signaling by activating SOS1.
研究领域:
肿瘤学
·
分子生物学
·
药物化学
✓ 已验证
DOI
PubMed
高影响因子
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