BIOMATERIALS
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2025
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IF 12.9
Nasha Qiu,Chang Xu,Zhen Zhang,Rui Wang,Xuyong Wei,Yangla Xie,Shuai Wang,Di Lu,Kai Wang,Shengjun Xu,Chenchen Shen,Renyi Su,Beini Cen,Yanpeng Liu,Youqing Shen,Xiao Xu
Effective cancer immune therapy requires the orchestration of antigen induction, presentation and T-cell activation, further enhanced by anti-angiogenesis treatment; therefore, multiple therapeutics are generally used for such combination therapy. Herein, we report esterase-hydrolysable cationic polymers, N -[3-((4-acetoxy benzyl) oxy)-3-oxopropyl]- N -methyl-quaternized PEI (ERP) and poly{ N -[2-(acryloyl-oxy) ethyl]- N -[p-acetyloxyphenyl]- N,N -dimethylammonium chloride} (PQDMA), capable of simultaneously inducing tumor cell immunogenic cell death (ICD) to release antigens, activating the cGAS-STING pathways of tumor macrophages and dendritic cells, and releasing antiangiogenic agent p -hydroxybenzyl alcohol (HBA). Thus, intratumoral injection of ERP or PQDMA systemically boosted the anti-cancer immunities and inhibited tumor angiogenesis in mouse hepatocellular carcinoma and melanoma bilateral tumor models, leading to more effective tumor growth inhibition of both treated and abscopal untreated tumors than ICD alone induced by mitoxantrone and control cationic polymers. The mechanism study of gene knockout mice and transcriptome sequencing analysis confirmed the involvement of cGAS-STING and type I IFN signaling pathways. This work demonstrates ERP and PQDMA as the first examples of inherent therapeutic polymers, accomplishing systemic tumor inhibition without combining other therapeutic agents.
研究领域:
生物医学工程
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免疫学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Drug Design Development and Therapy
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2023
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IF 4.8
Yi-Jin Wu,Sa-Sa Zhang,Qin Yin,Ming Lei,Qi-Hai Wang,Wen-Gang Chen,Ting-Ting Luo,Peng Zhou,Cong-Lan Ji
Background α-Mangostin (MG) showed the potentials in alleviating experimental arthritis, inhibiting inflammatory polarization of macrophages/monocytes, and regulating peroxisome proliferators-activated receptor γ (PPAR-γ) and silent information regulator 1 (SIRT1) signals. The aim of this study was to analyze the correlations among the above-mentioned properties.Methods Antigen-induced arthritis (AIA) was established in mouse, which was treated with MG in combination with SIRT1/PPAR-γ inhibitors to clarify the role of the two signals in the anti-arthritic actions. Pathological changes were systematically investigated. Phenotypes of cells were investigated by flow cytometry. Expression and co-localization of SIRT1 and PPAR-γ proteins in joint tissues were observed by the immunofluorescence method. Finally, clinical implications from the synchronous up-regulation of SIRT1 and PPAR-γ were validated by experiments in vitro.Results SIRT1 and PPAR-γ inhibitors (nicotinamide and T0070097) reduced the therapeutic effects of MG on AIA mice, and abrogated MG-induced up-regulation of SIRT1/PPAR-γ and inhibition of M1 polarization in macrophages/monocytes. MG has a good binding affinity to PPAR-γ, and MG promoted the co-expression of SIRT1 and PPAR-γ in joints. Synchronously activating SIRT1 and PPAR-γ was revealed to be necessary by MG to repress inflammatory responses in THP-1 monocytes.Conclusion MG binds PPAR-γ and excites this signaling to initiate ligand-dependent anti-inflammatory activity. Due to certain unspecified signal transduction crosstalk mechanism, it then promoted SIRT1 expression and further limited inflammatory polarization of macrophages/monocytes in AIA mice.
研究领域:
免疫学
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药理学
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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
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2022
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IF 10.383
Yafang Shen,Fei Jia,Aoming Liang,Yawen He,Yaping Peng,Huang Dai,Yingchun Fu,Jianping Wang,Yanbin Li
Exploring new functions of nanomaterials can help facilitate the development of biosensors for the detection of antibiotics. Herein, a new detection modality based on monovalent antigen-induced aggregation (MAA) of immunomagnetic beads (IMBs) was proposed for rapid and label-free detection of enrofloxacin (ENR), which endowed IMBs with the abilities of both sample separation and signal generation. In the presence of ENR, the initially well-dispersed IMBs were aggregated and the degree of aggregation was in a concentration-dependent manner. After exploring the mechanism underlying IMB aggregation and investigating the key parameters affecting it, a label-free biosensing platform was developed for rapid and sensitive detection of ENR. Based on the significant differences in the magnetic separation speed and size between the aggregated and well-dispersed IMBs, two methods were proposed for quantitatively determining ENR, i.e., measuring the turbidity of the IMB supernatant after magnetic separation for a given time and visualizing and calculating the grayscale value of the aggregated IMBs trapped on the surface of a nitrocellulose membrane. A three-dimensional (3D)-printed syringe was designed and fabricated for automatic filtration of IMBs. This immunosensor allowed for sensitive detection of ENR in less than 15 min without any labels. It exhibited a satisfactory limit of detection of 0.79 ng mL–1 and showed the feasibility for ENR detection of spiked chicken meat with recovery rates ranging from 74.8 to 98.3%. The MAA immunosensor can act as a promising tool to detect trace levels of ENR and has the potential to be applied to complex food samples.
研究领域:
分析化学
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生物传感
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纳米技术
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食品安全
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环境科学
✓ 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）