JOURNAL OF NANOBIOTECHNOLOGY
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2026
·
IF 12.6
Jinming Tian,Zeyu Zhang,Chao Cheng,Fei Yu,Tao Wang,Bin Cui,Ye Peng,Shuang Qiu,Fuming Wang,Weijing Cheng,Rong Luo,Guorong Jia,Changjing Zuo
Transarterial radioembolization (TARE) with β-emitting radionuclides is widely used for hepatocellular carcinoma (HCC), but its clinical efficacy remains to be further improved. α-particle-emitting radionuclides possess high linear energy transfer (LET) and unique advantages in cancer therapy, motivating α-particle based composite platform. Accordingly, we engineer the first clinically mimetic α-TARE microsphere by in-situ ²²³Ra-doped calcium-alginate composite microsphere (²²³Ra/Ca-ALG MS) using a hydrogel matrix, in which alginate "egg-box" coordination captures Ra²⁺ to provide stable radiolabeling, delivered via selective hepatic arterial injection to HCC. The microspheres exhibited excellent radiolabeling stability (88% retention after 384 h) and potent, dose-dependent cytotoxicity against HCC cells under hypoxia. In an orthotopic rat HCC model, 223 Ra/Ca-ALG MS-based TARE achieves precise intratumoral localization and sustained retention on SPECT/CT; ¹⁸F-FDG PET/CT and histopathology indicate a robust antitumor response, while serum biochemistry and histology support a favorable safety profile. Moreover, ²²³Ra/Ca-ALG MS provide powerful immune-activating capacity. Transcriptomics reveals activation of DNA-damage response, immunogenic cell death, and antigen-presentation pathways, flow cytometry and immunohistochemistry show increased dendritic-cell maturation and CD8⁺ T-cell infiltration. Collectively, 223 Ra/Ca-ALG MS demonstrates hypoxia-tolerant cytotoxicity, immune-activating potential, offering new insights for the development of immune-based TARE strategies in HCC and showing promising prospects for clinical translation.
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PubMed
高影响因子
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2023
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IF 3.4
Zhaomin Lu,Juan Liu,Liangjian Zhao,Chenli Wang,Feng Shi,Zhengqi Li,Xuesong Liu,Zhiwei Miao
Objective Polymer micelles were prepared (L-RSPMs) with luteolin and synthetic RA-SS-mPEG polymeric material before evaluation of their anti-inflammatory effect on 2, 4, 6-trinitro-benzene-sulfonic acid (TNBS)-induced ulcerative colitis (UC) model in rats.Methods The synthetic RA-SS-mPEG was characterized with NMR spectroscopy, before preparation of luteolin-coated RA-SS-mPEG polymer micelles. The in vitro characterization and evaluation of the formulation were accomplished, couple with its pharmacokinetic parameters. The levels of PEG2, MDA, CRP and GSH, as well as concentrations of TNF-α, IL1-β, IL-6 and IL-10 in serum and colon tissue were detected via ELISA kit. The degree of colon injury and inflammation was evaluated via histopathologic examination.Results L-RSPMs displayed small average droplet size (133.40 ± 4.52 nm), uniformly dispersed (PDI: 0.163 ± 0.011), good stability, slow release and enhanced solubility. We observed 353.28% increase in the relative bioavailability of L-RSPMs compared to free luteolin, while the half-life of the micelle was extended by 6.16h. Compared to model (M) group, luteolin (low and high doses) and L-RSPMs (low and high doses) significantly reduced levels of MDA, PEG2, CRP, TNF-α, IL-6 and IL-1β in colon tissue and serum of colitic rats but dose dependently increased IL-10 and SOD levels (p < 0.01). Histopathologic examination of colon showed that luteolin (low and high doses) and L-RSPMs (low and high doses) improved colonic inflammation in colitic rats to varying degrees compared to M group.Conclusion L-RSPMs could improve TNBS-induced colon inflammation by enhancing bioavailability, promoting antioxidant effects and regulating cytokine release, which may become a potential agent for UC treatment in clinical settings.
研究领域:
药剂学
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炎症研究
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药物递送系统
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PubMed
高影响因子
MOLECULES
·
2026
·Vol. 31
·期 10
·1560
·
IF 5.1
Sisi Huang,Wei Cai,Yan Wang,Xiaoliang Xing,Zaiqi Zhang
Objective:This study aimed to investigate whether pomolic acid (PA), a predicted bioactive metabolite of the Dong botanical drug Madeng’ai (MDA), suppresses inflammatory cytokine expression by inhibiting nuclear factor-κB (NF-κB) pathway activation in a tumor necrosis factor-α (TNF-α)-induced human rheumatoid arthritis fibroblast-like synoviocyte (RA-HFLS) model.Methods:PA content in MDA from different regions and harvest years was quantified via High-Performance Liquid Chromatography (HPLC). Network analysis was employed as a hypothesis-generating tool to predict potential targets and pathways, followed by molecular docking to validate the binding affinity of PA to core targets of the NF-κB pathway, and ADMET prediction to evaluate its pharmacokinetic properties and safety profile. The RA-HFLS inflammatory model was induced by TNF-α. Cell viability and inflammatory cytokine secretion were assessed using Cell Counting Kit-8 (CCK-8) and enzyme-linked immunosorbent assay (ELISA). NF-κB signaling pathway activation and downstream gene expression were examined by Western blot and reverse transcription quantitative polymerase chain reaction (RT-qPCR), respectively.Results:HPLC analysis revealed that MDA samples from Guizhou harvested in 2019 contained the highest PA content (0.1117 mg/g). Network analysis predicted the NF-κB signaling pathway as a candidate mechanism underlying PA’s potential anti-inflammatory effects. Molecular docking showed that PA stably bound to IKKβ, p65, and IκBα, while ADMET prediction indicated favorable intestinal absorption, low drug–drug interaction risk, and good genetic safety, albeit with potential hepatotoxicity and reproductive toxicity risks. In the TNF-α-induced RA-HFLS model, PA dose-dependently inhibited abnormal cell proliferation and significantly reduced the secretion of pro-inflammatory cytokines TNF-α and interleukin-6 (IL-6). Mechanistic studies indicated that PA suppressed the activation of the NF-κB signaling pathway, thereby downregulating the mRNA expression of inflammatory genes such as IL-6, TNF-α, and interleukin-1β (IL-1β).Conclusions:PA, a bioactive metabolite of the Dong botanical drug MDA, may inhibit NF-κB signaling pathway activation, thereby downregulating TNF-α-induced inflammatory cytokine expression in RA-HFLS, demonstrating its in vitro anti-inflammatory potential.
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高影响因子
MOLECULAR PHARMACEUTICS
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2025
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IF 4.5
Hongyu Zhu,Sen Yang,Jingyang Zhao,Liuyang Wang,Chenghao Gao,Yanan Sheng,Xuan Lin,Zhiguo Su,Kiichi Sato,Zhongyu Hu,Songping Zhang
All-trans retinoic acid (Ra) has been demonstrated to enhance the establishment of systemic and intestinal immunity for codelivered antigens; however, the extremely poor water solubility of Ra significantly limits its application in vaccines. Herein, leveraging the advantages of ionic liquids in modifying the physicochemical properties of small-molecule drugs, we synthesized a novel ionic liquid composed of choline and retinoic acid ([Cho][Ra]). Compared to Ra, [Cho][Ra] exhibited an 18165-fold increase in solubility at pH 7.4 and an acid-responsive Ra release behavior. The [Cho][Ra] was then formulated with the SARS-CoV-2 RBD antigen, and its adjuvant effects were comprehensively evaluated. The in vitro cellular studies indicated that at 50 μg Ra equivalent dose, the [Cho][Ra]@RBD showed significantly higher than RBD along in activation of BMDC and the expression of gut homing molecules, including C–C motif chemokine receptor 9 (CCR9, 10.55 folds), α4β7 integrin (13.29 folds), and lymph node migration molecule CCR7 (82.68 folds). Animal experiments showed that compared to RBD alone, [Cho][Ra]@RBD promoted the establishment of mucosal immunity in the intestines in mice at the early stage following subcutaneous immunization and elicited higher serum antibody levels. Furthermore, compared to RBD and Alum@RBD, [Cho][Ra]@RBD enhanced the formation of CD4+ TCM and CD8+ TCM cells, indicating stronger cellular immune responses. In summary, [Cho][Ra] showed potential adjuvant effects in enhancing the humoral and cellular immune responses, as well as in the establishment of intestinal mucosal immunity for RBD antigen without the need for delivery system, thereby offering promising prospects for applying Ra in vaccines.
研究领域:
免疫学
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药剂学
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分子药理学
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疫苗学
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纳米医学
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药物递送
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转化医学
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PubMed
高影响因子
FOOD CHEMISTRY
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2024
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IF 8.5
Xiaomeng Li,Mengyao Wu,Minquan Xia,Mohamed Salama,Haoyang Sun,Lixian Ding,Xi Huang,Dewei Shu,Zhaoxia Cai
This work presents a novel use of fibrous egg white protein (FEWP) in food preservation and nutraceutical applications. In this study, food-grade FEWP was used as an encapsulating material, along with chitosan (CS), to stabilize emulsions. The emulsion system was then used as a delivery system to improve the stability of retinyl acetate (RA). The structural and functional properties, as well as the stability and rheological behavior of the FEWP/CS copolymer, was investigated. The stability of RA-enriched emulsions was also evaluated. FEWP and CS stabilized emulsions exhibited smaller particle sizes and enhanced stability against different ionic strengths and storage periods. Additionally, RA-encapsulated emulsions stabilized by FEWP:CS (25:1 w /w) effectively inhibited apple browning. This study presents a promising strategy for delivering antioxidant components, highlighting its potential in food preservation and nutraceutical applications.
研究领域:
食品科学
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营养学
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材料科学
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PubMed
高影响因子
ACS Sustainable Chemistry & Engineering
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2020
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IF 7.632
Xuemei Li,Junying Tian,Hailong Liu,Xun Hu,Jia Zhang,Chungu Xia,Jing Chen,Haichao Liu,Zhiwei Huang
The reductive amination (RA) of 2-hydroxytetrahydropyran (2-HTHP) produced from biofurfural-derived dihydropyran provides a new efficient process for the clean synthesis of valuable 5-amino-1-pentanol (5-AP). Among various solid catalysts tested, the inexpensive Ni–Mg3AlOx catalysts derived from hydrotalcite precursors were found to be very active and selective, especially at Ni loadings above 20 wt %. A 85% total yield of 5-AP was obtained from dihydropyran on 40Ni–Mg3AlOx, the catalyst with the highest 2-HTHP RA activity among the Ni–Mg3AlOx catalysts, under mild conditions of 60 °C and 2 MPa H2. Characterization results showed that the reducibility of the calcined NiO-Mg3AlOx samples increased with increasing Ni loading from 5 to 50 wt %, while the Ni0 crystallite sizes exhibited a minimum of 4.8 nm on 40Ni–Mg3AlOx after reduction in H2 at 750 °C. The volcanic changes of 5-AP generation rate/yield with increasing Ni loading of the Ni–Mg3AlOx catalysts and with rising prereduction temperature of 30Ni–Mg3AlOx catalyst in 2-HTHP RA indicate that the balance of the reducibility and Ni0 particle size of the catalysts played an important role in obtaining high 5-AP yields. The 30Ni–Mg3AlOx catalyst showed a good stability in 2-HTHP RA examined in a continuous flow reactor over a 90 h time-on stream.
研究领域:
化学工程
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催化
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绿色化学
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生物化工
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高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2021
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IF 4.36
Yanping Jiang,Yongfeng Zheng,Qin Dong,Wan Liao,Lan Pang,Jiao Chen,Qinman He,Jinming Zhang,Yuanhong Luo,Jiaxin Li,Chaomei Fu,Qiang Fu
Ethnopharmacological relevance Shentong Zhuyu decoction (STZYD) was first recorded in the classic of “ Yilin Gaicuo ” written by Wang Qingren, and recognized by the Chinese National Administration of Traditional Chinese Medicine as one of the 100 classic formulas. The formula has been widely used in the treatment of rheumatoid arthritis (RA) with significant clinical effects. However, its mechanism of action is not completely clear. Aim of the study This study aimed to explore the mechanism of STZYD in the treatment of RA by network pharmacology and metabolomics. Materials and methods The effects of STZYD anti-RA were investigated by paw swelling, arthritis score, cytokine level, histopathological and micro-CT analysis in adjuvant-induced arthritis (AIA) rats. The chemical constituents of STZYD and absorbed constituents in AIA rat serum were analyzed by UPLC-Q-Exactive MS/MS. Based on the characterized chemical components, the network pharmacology was used to find potential targets and signaling pathways of STZYD in RA treatment. Meanwhile, the predicted pathway was determined by the Western blot (WB). Subsequently, non-targeted metabolomics of serum was performed to analyze metabolic profiles, potential biomarkers, and metabolic pathways of STZYD in the treatment of RA based on LC-MS technology. Results STZYD significantly alleviated RA symptoms by improving paw redness and swelling, bone and cartilage damage, synovial hyperplasia , and infiltration of inflammatory cells, and decreased the generation of pro-inflammatory cytokines IL-1β, IL-6, IL-17A and TNF-α in AIA rats. Totally, 59 chemical components of STZYD and 24 serum migrant ingredients were identified. A total of 655 genes of potential bioactive components in STZYD and 1025 related genes of RA were obtained. TNF signaling pathway was considered to one of the main signaling pathways of STZYD anti-RA by KEGG analysis, including a wide range intracellular signaling pathways. NF-κB signaling pathway regulates inflammation and immunity in the TNF signaling pathway. STZYD markedly inhibited the expression of NF-κB signaling pathway. Ten potential biomarkers were found in metabolomics based on LC-MS technology. Alanine , aspartate and glutamate metabolism, arachidonic acid metabolism are the most related pathways of STZYD anti-RA. Conclusion The study based on serum pharmacochemistry, network pharmacology and metabolomics indicated that STZYD can improve RA through regulating inflammation and immunity related pathways, and provided a new possibility for treatment of RA.
研究领域:
药理学
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中医
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免疫学
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风湿病学
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代谢组学
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网络药理学
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PubMed
高影响因子
JOURNAL OF MATERIALS SCIENCE
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2023
·Vol. 58
·期 21
·8952-8968
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IF 4.5
Qi Wenxia,Wang Shenglan,Yang Heng,Luo Tingting,Zhao Feng,Han Jingtian,Zhang Jing
Combination chemotherapy is a crucial therapeutic strategy to improve the therapeutic efficacy of breast cancer in clinic. When combined with photodynamic therapy (PDT), the therapeutic efficacy can be further enhanced not only by PDT-induced phototoxicity, but also by PDT-induced photochemical internalization which facilitates the intracellular delivery and endo/lysosomes escape of drugs, therefore exhibit considerable potential in clinical treatment of breast cancer. Herein, a novel cocktail therapeutic strategy based on albumin-based nanosystem was established by covalently modifying human serum albumin (HSA) with all-trans retinoic acid (RA) and chlorin e6 (Ce6) to form HSA-RA-Ce6 (HRC) conjugate, and using paclitaxel (PTX) to induce self-assembly of HRC to form HRC@PTX nanoparticles (HRC@PTX NPs). The HRC@PTX NPs could amplify the therapeutic efficacy of combination chemotherapy of RA and PTX with Ce6-mediated PDT. The HRC@PTX NPs were characterized with a mean particle size of 174.1 ± 2.1 nm and a slightly negative zeta potential and exhibited good stability and hemocompatibility. The HRC@PTX NPs could promote the cellular uptake of drugs by MCF-7 cells and MDA-MB-231 cells and produce ROS to amplify the synergistic anti-tumor efficacy. The in vitro inhibitory effects on tumor growth investigated on monolayer and three-dimensional tumor spheroids revealed that HRC@PTX NPs exhibited significantly higher anti-tumor activity when exposed to 660-nm laser. These results demonstrated that HRC@PTX NPs could be developed as a promising cocktail therapeutic strategy for synergistic breast cancer therapy. Graphical abstract
研究领域:
肿瘤学
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药学
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纳米技术
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癌症治疗
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DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2022
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IF 8.025
Shang Qiu,Xiunan Wu,Dechun Geng,Wenzhen Pan,Zheng Li,Gang Wang,Daen Li,Cheng Li,Shuo Feng,Liang Zhu,Yaozeng Xu,Fenglei Gao
Cannabinoid receptors are widely distributed in many cells in Rheumatoid arthritis RA and strengthening factor to boost the development of RA diseases. Here, the hollow mesoporous copper sulfide (CuS) was used as the carrier skeleton and the cannabinoid type 2 (CB2) receptor agonist JWH133 was efficiently loaded inside of CuS through adsorption, then the outer layer was modified with hyaluronic acid (HA) to prevent the leakage of internal drugs. After the [email protected] nano carrier reached the target area, HA responsive cracked under RA microenvironment to realize the first step of accurate drug delivery of JWH133, and the thermally responsive CuS under near-infrared (NIR) promoted the release of internal drugs. Then, JWH133 specifically combined CB2 receptors on the surface of macrophage, synovial cells and osteoblasts to realize the second step of drug delivery. The inflammatory factors secreted by cells are significantly inhibited, and the activity of osteoblasts was significantly enhanced. Therapeutic effect by [email protected] of RA was well verified by decreasing levels of inflammation in vivo and improvement of inflamed and swollen joints of mice. The [email protected] nanocomposite showed satisfactory multidimensional therapeutic effect of RA in vitro and in vivo , which provided a novel idea for RA treatment.
研究领域:
纳米技术
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药学
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风湿病学
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诊疗学
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PubMed
高影响因子
CHEMISTRY OF MATERIALS
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2019
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IF 10.159
Guojun Zhou,Xingxing Jiang,Maxim Molokeev,Zheshuai Lin,Jing Zhao,Jing Wang,Zhiguo Xia
Finding new low-dimensional metal halides with broad-band emission is attracting interest in single-component phosphor for white light-emitting diodes (WLEDs). The full-spectrum white light still remains a challenge as found in the two-dimensional hybrid material (C6H18N2O2)PbBr4 exhibiting the intrinsic free exciton (FE) and broad-band self-trap exciton (STE) emission upon 365 nm ultraviolet excitation, and a combined strategy has been proposed through doping the Mn2+ ions enabling a superposition of multiple emission centers toward the ultra-broad-band warm white light. The occupation of Mn2+ in (C6H18N2O2)PbBr4 has been discussed, and optical investigations verify that the warm white-light emission of Mn2+-doped (C6H18N2O2)PbBr4 originates from the coupling effects of the FE, STEs, and the 4T1–6A1 transition of the doped Mn2+. When the concentration of Mn2+ is 5%, the emission spectrum of the phosphor covers all visible-light areas with a full width at half maximum (FWHM) of about 230 nm. The high Ra (84.9) and warm light CCT (3577 K) values of the as-fabricated WLED lamp demonstrate that (C6H18N2O2)Pb1–xMnxBr4 can be promising as single-component white-light phosphor in solid-state lighting. Our work could provide a new understanding and perspective about hybrid metal halides for designing superior phosphor toward single-component white emission.
研究领域:
材料科学
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光电
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固态照明
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高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2020
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IF 3.69
Li Yang,Ronghua Liu,Aiguo Fan,Guoyue Zhong,Junwei He
Ethnopharmacological relevance The root of Dendropanax dentiger (Harms) Merr. is a pivotal folk Chinese medicine against rheumatoid arthritis (RA) with no scientific validation. Aim of the study This study was conducted to explore the anti-RA effect of the D. dentiger extract on complete Freund's adjuvant-induced arthritis (AIA) in rats and identified its major bio-constituents. Materials and methods Dendropanax dentiger roots extracts (127.5, 255.0 and 510.0 mg/kg, once daily) were orally at day 7 post-administration adjuvant and lasting for 22 days. The therapeutic effects of D. dentiger roots extract on AIA rats were investigated by body weight growth, arthritis score, thymus and spleen indices, and histopathological analysis. Moreover, the levels of rheumatoid factor (RF), C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), IL-4, IL-6, IL-10, IL-17, cyclooxygenase-2 (COX-2), 5-lipoxygenase (5-LOX) and matrix metalloproteinase-2 (MMP-2) were also evaluated. Finally, the major constituents were isolated and identified from D. dentiger roots extract with COX-2 inhibitory and antioxidant activities . Results Dendropanax dentiger roots extract remarkably alleviated the histological lesions of knee joint, increased body weight growth, decreased arthritis score, and reduced thymus and spleen indices in model rats. In parallel, the levels of RF, CRP, TNF-α, IL-1β, IL-6, IL-17, COX-2, 5-LOX and MMP-2 were observably downregulated, while the levels of IL-4 and IL-10 were prominently upregulated in D. dentiger roots extract-treated rats. Meanwhile, 14 compounds were isolated and identified from D. dentiger roots extract, and four phenol derivatives ( 1 , 4 , 6 and 7 ) exhibited remarkable COX-2 inhibitory and antioxidant activities. Conclusions Dendropanax dentiger roots extract possessed persuasive anti-RA effect may be partly responsible for phenol derivatives via modulation of inflammatory biomarkers, and supports the traditional folk use of D. dentiger in China.
研究领域:
药理学
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免疫学
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民族药理学
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风湿病学
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DOI
PubMed
高影响因子
International Journal of Nanomedicine
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2023
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IF 8
Yuling Liu,Xin Nie,Yihan Wu,Longfei Lin,Qian Liao,Jingjing Li,Simon Ming-Yuen Lee,Hui Li,Jinming Zhang
Introduction: The insufficient targeting delivery of therapeutic agents greatly impeded the treatment outcomes of rheumatoid arthritis (RA). Despite the recognized therapeutic advantages of gambogic acid (GBA) in inflammatory diseases, its high delivery efficiency to inflammatory site still limits its clinical application. Self-assembly of drug dimers into carrier-free nanoparticles (NPs) has become a straightforward and attractive approach to develop nanomedicines for RA treatment. Herein, homodimers of GBA were designed to form the carrier-free NPs by self-assembly for RA treatment.
Methods: The synthetic gambogic acid dimers (GBA2) were self-assembled into NPs using a one-step solvent evaporation method. The size distribution, morphology, drug-loading efficiency (DLE) and storage stability were evaluated. A molecular dynamic simulation was conducted to gain further insight into the self-assembly mechanisms of GBA2/NPs. Besides, we investigated the cytotoxicity, apoptosis and cellular uptake profiles of GBA2/NPs in macrophages and osteoclasts. Finally, the specific biodistribution on the ankles of adjuvant-induced arthritis (AIA) mice, and the anti-RA efficacy of the AIA rat model were assessed.
Results: GBA2/NPs exhibited the uniform spherical structure, possessing excellent colloidal stability, high self-assembly stability, high drug loading and low hemolytic activity. Comparing with GBA, GBA2/NPs showed higher cytotoxicity, cellular uptake and apoptosis rate against osteoclasts. In addition, GBA2/NPs exhibited much higher accumulation in ankle joints in vivo. As expected, the systematic administration of GBA2/NPs resulted in the greater alleviation of arthritic symptoms, cartilage protection, and inflammation, notably the reduced systemic toxicity compared to free GBA.
Conclusion: GBA2/NPs formed GBA dimers exhibited the superior accumulation in the inflamed joint and anti-RA activity, potentially attributing to the similar extravasation through leaky vasculature and subsequent inflammatory cell-mediated sequestration (""ELVIS"") effects in inflamed joint and the enhanced cellular uptake in macrophages and osteoclasts. Our findings provide substantial evidence that self-assembly of GBA2/NPs would be a promising therapeutic alternative for RA treatment.
研究领域:
药学
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纳米技术
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风湿病学
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药物递送系统
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炎症研究
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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）