International Journal of Nanomedicine
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2023
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IF 8
Shaoyin Wei,Sijie Zhou,Wenjuan Huang,Xingjie Zan,Wujun Geng
Purpose There has been a substantial global market for antibodies, which are based on extracellular targets. Binding intracellular targets by antibodies will bring new chances in antibody therapeutics and a huge market increase. We aim to evaluate the efficiency of a novel delivery system of His6-metal assembly (HmA) in delivering intracellular antibodies and biofunctions of delivered antibodies.Methods In this study, the physicochemical properties of HmA@Antibodies generated through co-assembling with antibodies and HmA were well characterized by dynamic light scatter. The cytotoxicity of HmA@Antibodies was investigated by Cell Counting Kit-8 (CCK-8). The endocytic kinetics and lysosome escape process of HmA@Antibodies were studied by flow cytometry and fluorescent staining imaging, respectively. Compared to the commercialized positive control, the intracellular delivery efficiency by HmA@Antibodies and biofunctions of delivered antibodies were evaluated by fluorescent imaging and CCK-8.Results Various antibodies (IgG, anti-β-tubulin and anti-NPC) could co-assemble with HmA under a gentle condition, producing nano-sized (~150 nm) and positively charged (~+30 eV) HmA@Antibodies particles with narrow size distribution (PDI ~ 0.15). HmA displayed very low cytotoxicity to divers cells (DCs, HeLa, HCECs, and HRPE) even after 96 h for the feeding concentration ≤100 μg mL−1, and fast escape from endosomes. In the case of delivery IgG, the delivery efficiency into alive cells of HmA was better than a commercial protein delivery reagent (PULSin). For cases of the anti-β-tubulin and anti-NPC, HmA showed comparable delivery efficiency to their positive controls, but HmA with ability to deliver these antibodies into alive cells was still superior to positive controls delivering antibodies into dead cells through punching holes.Conclusion Our results indicate that this strategy is a feasible way to deliver various antibodies intracellularly while preserving their functions, which has great potential in various applications and treating many refractory diseases by intracellular antibody delivery.
研究领域:
药理学
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分子生物学
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治疗学
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DOI
PubMed
高影响因子
Advanced Science
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2023
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IF 15.1
Sijie Zhou,Ruhui Yang,Xiaoling Xie,Liwen Wang,Shengwu Zheng,Na Li,Sicheng Tang,Xingjie Zan
Diabetes has been listed as one of the three major diseases that endanger human health. Accurately injecting insulin (Ins) depending on the level of blood glucose (LBG) is the standard treatment, especially controlling LBG in the long-term by a single injection. Herein, the pH-responsive hexa-histidine metal assembly (HmA) encapsulated with enzymes (GOx and CAT) and Ins (HmA@GCI) is engineered as the vehicle for glucose-mediated insulin delivery. HmA not only shows high proteins loading efficiency, but also well retained proteins activity and protect proteins from protease damage. Within HmA, the biocatalytic activities of enzymes and the efficiency of the cascade reaction between GOx and CAT are enhanced, leading to a super response to the change of LBG with insulin release and efficient clearance of harmful byproducts of GOx (H 2 O 2 ). In the treatment of diabetic mice, HmA@GCI reduces LBG to normal in half an hour and maintains for more than 5 days by a single subcutaneous injection, and nearly 24 days with four consecutive injections. During the test period, no symptoms of hypoglycemia and toxicity to tissues and organs are observed. These results indicate that HmA@GCI is a safe and long-acting hypoglycemic agent with prospective clinical application.
研究领域:
药学
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生化
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生物医学工程
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糖尿病研究
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PubMed
高影响因子
Materials Today Bio
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2023
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IF 8.2
Qing Shi,Xingxing Zhang,Minmin Wu,Yuhan Xia,Yating Pan,Jialu Weng,Na Li,Xingjie Zan,Jinglin Xia
Lipiodol-based transcatheter arterial chemoembolization (TACE) is currently the predominant and first-line treatment option recommended by the global standard for unresectable hepatocellular carcinoma (HCC). However, the unstable emulsion of Lipiodol causes a substantial proportion of chemotherapy drugs to enter the circulation system, leading to poor accumulation in cancer tissues and unexpected side effects of chemotherapy drugs. Herein, we emulsified Lipiodol with a pH-sensitive drug delivery system assembled from hexahistidine and zinc ions (HmA) with a super-high loading capacity of doxorubicin (DOX) and a promising ability to penetrate bio-barriers for the effective treatment of HCC by TACE. In vitro tests showed that DOX@HmA was comparable to free DOX in killing HCC cells. Impressively, during the in vivo TACE treatment, the anti-tumor efficacy of DOX@HmA was significantly greater than that of free DOX, indicating that DOX@HmA increased the accumulation of DOX in tumor. Emulsifying Lipiodol with pH-sensitive DOX@HmA significantly inhibited cell regeneration and tumor angiogenesis and decreased the systemic side effects of chemotherapy, especially by suppressing pulmonary metastasis in liver VX2 tumors in rabbits by inhibiting epithelial–mesenchymal transition (EMT). Emulsifying tumor microenvironment-responsive drug delivery systems (DDSs) with Lipiodol could be a new strategy for clinical TACE chemotherapy with potentially enhanced HCC treatment.
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PubMed
高影响因子
ANALYTICAL SCIENCES
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2023
·Vol. 39
·期 7
·1171-1178
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IF 1.6
Wang Kun,Gao Xue,Chen Jianfeng,Yang Xiaoyan
Abstract In this study, a sensitive photoelectrochemical immunosensor with dye-enhanced anodic photocurrent response was proposed for sensitive detection of α-fetoprotein (AFP). Specifically, europium-doped TiO 2 (Eu-TiO 2 ) was used as the photoelectrochemical functional material and coated onto indium tin oxide (ITO) electrode. Doxorubicin (DOX) as an excellent fluorescent dye was encapsulated in the hydrophobically modified alginate (HMA). Then the dye-loaded HMA was modified onto the surface of Eu-TiO 2 to further sensitize the photocurrent response. The results showed that the photoelectrical signal was enhanced and stabilized due to the effect of sensitization of DOX on Eu-TiO 2 material. The constructed PEC sensor revealed a good linear response to AFP antigen ranging from 0.5 to 100 ng/mL with a detection limit of 0.41 pg/mL. The clinical patient’s serum test results obtained from the proposed PEC immunosensor were consistent with those obtained from the commercial electrochemilunescence assay. The proposed PEC sensing method could be a promising analytical tool for the detection of AFP in clinical analysis. Graphical abstract
研究领域:
生物医学工程
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分析化学
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PubMed
高影响因子
SCIENTIA HORTICULTURAE
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2020
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IF 2.769
Yu Tao Huang,Shu Yu Cai,Xiao Li Ruan,Shan Yu Chen,Gao Fu Mei,Guan Hai Ruan,Dong Dong Cao
Zinc (Zn 2+ ) stress is an important abiotic constraint affecting crop seed germination and plant growth. It is vital to exploit and utilize zinc-polluted soil by exploring technologies for promoting seed germination under Zn 2+ stress. This study aims to explore the effects of salicylic acid (SA) and 2-aminoindan-2-phosphonic acid (AIP, SA synthesis inhibitor) on the Zn 2+ stress resistance of sunflower during seed germination. Zn 2+ treatment significantly inhibited seed germination and seedling growth of sunflower. In addition, Zn 2+ treatment increased Zn 2+ and abscisic acid (ABA) contents, while decreased SA and gibberellins (GA) contents of sunflower seeds. Exogenous SA effectively alleviated the inhibition of Zn 2+ stress on sunflower seed germination, promoted endogenous SA anabolism, and increased the expression of zinc transporter-related genes family ( MTP and HMA ), which leading to decreased Zn 2+ accumulation. Moreover, exogenous SA increased GA content and decreased ABA content by regulating the gene expressions of metabolic related enzymes. On the contrary, AIP treatment further aggravated the inhibitory effect of Zn 2+ stress on sunflower seed germination. This study demonstrated that exogenous SA could affect the Zn 2+ metabolic balance in sunflower seeds by regulating the expression of Zn 2+ transport-related gene ( MTP and HMA ), promote the biosynthesis of endogenous SA and GA, inhibit the accumulation of ABA content, and improve the germination ability of sunflower seed under zinc stress.
研究领域:
植物生理学
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环境科学
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农学
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DOI
高影响因子
PROGRESS IN ORGANIC COATINGS
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2024
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IF 6.5
Biru Shi,Xiaoling Xu,Jiahui Zhong,Zhenyu Zhang,Haosen Ma,Yu He,Xinxin Tian,Yan Zhou,Xiangdong Liu,Dekun Sheng,Yuming Yang
Hot-melt adhesive (HMA) is commonly used in industrial manufacturing due to its ease of use. However, the direct factors that affect shear strength have been unclear in recent years, making it difficult to prepare hot melt adhesives with high shear strength, which are mostly lower than 6 MPa. In this study, three types of polyurethane HMAs, differing in the position of H-bond motifs, ureidopyrimidinone (UPy), were synthesized and characterized, the most central factor for shear strength, Young's modulus , was firstly found out and proved. Side-chain UPy provides better flexibility and more chain entanglement . The lap shear strength of SPU was about 13.48 MPa, which was the highest shear strength of PU HMA, and remained 73.4 % even after 4 cycles. Compared to the other two samples, the side-chain motifs improved the possibility of forming hydrogen bonds with adherends and increased chain mobility. This led to a more efficient wetting process and strengthened Young's modulus directly, enhancing adhesive property incomparably. This work provides a satisfactory method for achieving high shear strength in HMA.
研究领域:
材料科学
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化学工程
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聚合物科学
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DOI
高影响因子
BIOCONJUGATE CHEMISTRY
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2020
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IF 4.031
Pengyan Hao,Xiaoxiao Wu,Liwen Wang,Shaoyin Wei,Hongyan Xu,Wenjuan Huang,Yana Li,Tinghong Zhang,Xingjie Zan
Utilizing nanoparticles to deliver subunit vaccine is considered to be a promising strategy to improve immune response. However, currently reported systems suffered from one or more points, for example, delicate design on molecular structures and elaborate synthesis process, low antigen and/or adjuvant encapsulation efficiency, involvement of toxic materials, and denaturing of bioactivity of antigen and/or adjuvant. To address these issues, here, for the first time, we developed a one-pot method to produce a subunit vaccine by using hexa-histidine metal assembly (HmA) to codeliver tumor-associated antigens (GP100, a peptide KTWGQYWQV) and adjuvant (CpG). The generation of subunit vaccines was detailedly characterized by various techniques, including dynamic scatter, scanning electron microscopy, transmission electron microscopy, UV–visible spectroscopy, agarose gel electrophoresis, etc. HmA displayed high efficiency on encapsulating both subunits (GP100 and CpG) under mild conditions, and the generated subunit vaccine showed a pH-dependent release profile of loaded subunits. In the cellular tests, these subunit vaccines behaved with a quick endocytosis into immune cells and a fast endo/lysosomes escape, inducing maturation of antigen presentative cells and stimulating a potent cellular immune response. These results suggested that HmA is a robust platform for fabricating subunit vaccine, with immense potential for the immunotherapy of various diseases.
研究领域:
纳米技术
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免疫学
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药学
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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）