BIOORGANIC & MEDICINAL CHEMISTRY
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2025
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IF 3
Lumei Dai,Shifang Wen,Yaling Chen,Xinchun Li,Bing Zhao,Xinyu You,Rongqiang Li,Bin Zhang
Self-assembled nanodrug conjugates utilize both hydrophilic and hydrophobic ligands for targeted tumor delivery, reducing systemic toxicity while enhancing therapeutic efficacy. Herein, four novel nonsteroidal anti-inflammatory drug (NSAID)-irinotecan (Ir) conjugates were synthesized by forming ester bonds between hydrophobic NSAIDs and hydrophilic Ir. These amphiphilic conjugates self-assembled into carrier-free NSAID-Ir nanoparticles (NPs) in aqueous solution. Among them, Ibu-Ir NPs demonstrated superior activity against HT-29 cells (IC 50 = 1.15 μM), showing 5.6-fold greater potency than free Ir. Mechanistically, Ibu-Ir NPs downregulated cyclooxygenase-2 and topoisomerase I expression, enhancing Ir's therapeutic effect. In HT-29 xenograft models, Ibu-Ir NPs was able to inhibit tumor growth, although the small sample size ( n = 3) carries a high risk of statistical errors. This simple yet potent strategy combines anti-inflammatory and anticancer actions, demonstrating significant potential for colorectal cancer therapy.
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CARBOHYDRATE POLYMERS
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2024
·
IF 10.7
Shuiling Qin,Zhiwei Wen,Huajie Huang,Wei Wu
Our research aimed to enhance the oral bioavailability of doxorubicin hydrochloride (DOX·HCl) while minimizing the potential for myocardial toxicity. To achieve this goal, we developed a new method that utilizes a coating material to encapsulate the drug in liposomes, which can specifically target intestinal taurine transporter proteins. This coating material, TAU-CS, was created by combining taurine with chitosan. We characterized TAU-CS using various methods, including 1 H NMR, FT-IR, and scanning electron microscopy (SEM). The resulting liposomes exhibited a regular spherical morphology, with a particle size of 195.7 nm, an encapsulation efficiency of 91.23 %, and a zeta potential of +11.65 mV. Under simulated gastrointestinal conditions, TAU-CS/LIP@DOX·HCl exhibited good stability and slow release. Pharmacokinetic studies revealed that, compared with DOX·HCl, TAU-CS/LIP@DOX·HCl had a relative bioavailability of 342 %. Intracellular uptake, immunofluorescence imaging, and permeation assays confirmed that the taurine transporter protein mediates the intestinal uptake of these liposomes. Our study suggested that liposomes coated with TAU-CS could serve as an effective oral delivery system and that targeting the taurine transporter protein shows promise in enhancing drug absorption.
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COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2025
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IF 5.4
Hongdong Song,Yaqiong Chen,Ruihan Huang,Xiao Guan
To enhance the oral bioavailability and hypoglycemic effect of insulin, we developed a novel bilayer liposome delivery system in this study. The outer layer of this system was decorated with propanoic acid-functionalized chitosan (CS/PA) to improve gastrointestinal stability and facilitate intestinal targeting of mono-carboxylate transporter protein 1 (MCT1). We encapsulated insulin in this newly developed delivery system. The CS/PA coating significantly enhanced the protective effect of liposomes on insulin in the gastrointestinal environment. Experiments using Caco-2 cells and ligated intestinal loops showed that IN-LIP-CS/PA facilitated insulin absorption and increased intestinal permeability. Importantly, MCT1-mediated energy-dependent endocytosis played a crucial role in the absorption process. Additionally, endocytosis of IN-LIP-CS/PA was mediated through clathrin, lipid raft, caveolin, and macropinocytosis. Furthermore, the endoplasmic reticulum and Golgi apparatus were mainly involved in the intracellular transport of IN-LIP-CS/PA. The combination of MCT1-mediated endocytosis and the intracellular transport pathways may help IN-LIP-CS/PA avoid lysosomal degradation, thereby improving the intracellular transport efficiency of insulin. In vivo studies demonstrated that IN-LIP-CS/PA achieved a significantly better hypoglycemic effect. These findings suggested that the newly developed bilayer liposome delivery system holds promise as an effective platform for the oral delivery of insulin.
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ACS Sustainable Chemistry & Engineering
·
2025
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IF 7.3
Xiaoyan Han,Shan Wang,Tingting Cui,Yumin Yang,Haixiang Li,Haiwen Zhang,Huanhuan Zhou,Xiaoxia Li
Aristolochic acid I (AA-I), a known nephrotoxin and carcinogen, is commonly found in certain medicinal plants, posing significant safety concerns. In this work, defect-engineered, molecularly imprinted UiO-66-NH2 was synthesized via a one-pot hydrothermal method using indomethacin (IND) as a green alternative template. The resulting imprinted metal–organic framework effectively mitigates matrix interference, enabling highly selective recognition and the efficient adsorption of AA-I. Structural characterization confirmed that the imprinting process and template removal did not compromise the framework integrity of UiO-66-NH2. Spectroscopic analysis revealed that AA-I recognition was governed by Zr coordination, electrostatic interactions, and spatially confined recognition sites within the porous framework. Density functional theory calculations further elucidated the interaction mechanisms involved in the adsorption process. The imprinted UiO-66-NH2 exhibited a maximum adsorption capacity of 42.74 mg/g and an imprinting factor of 2.48. In real sample analysis, the material achieved recovery rates of 96.7–103.5% and excellent selectivity in Clematis armandii extracts. The adsorption efficiency remained above 80% after five adsorption–desorption cycles, indicating good structural stability and reusability. This work offers a promising and sustainable strategy for improving herbal medicine safety through the rational design of ecofriendly MOF-based adsorbents.
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Crystals
·
2025
·Vol. 15
·期 6
·512
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IF 2.4
Shixin Fan,Wenling Zheng,Shizhao Ren,Wangchuan Xiao,Fenghua Chen,Rongrong Xue
Amorphous solid dispersion (ASD) technology is popularly used for enhancing the solubility of poorly water-soluble drugs. Drug molecules in ASDs can be dispersed in the form of either amorphous (AASD) or molecular (MASD) forms. The boundary between AASDs and MASDs (A–M boundary) is defined as the drug concentration at which the existence of MASDs obviously influences the physicochemical properties of ASDs. In this work, fluorescence spectroscopy based on the aggregation-caused quenching (ACQ) phenomenon was used to determine the A–M boundary of curcumin (CUR) ASDs prepared via neat ball milling. The relationship between the fluorescence intensity and the loading of CUR in the sample is consistent with the Stern–Volmer equation. For the CUR ASDs with PVP, the samples with CUR loading below 10% show significantly increased fluorescence and have a higher solubility (~178 μg·mL−1), suggesting the A–M boundary is around 10%. Similar A–M boundaries around 10% were also observed for CUR ASDs with PVPVA, Soluplus, HPMC, and HPMCAS. It is of great significance to define the A–M boundary of ASDs for guiding pharmaceutical ASD formulas by balancing drug loading, stability, and solubility.
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Nature Communications
·
2025
·Vol. 16
·期 1
·1-20
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IF 15.7
Zhang Zehong,Wan Qianyi,Zhu Yuedan,Ye Jinbao,Fu Fang,Fan Xinxin,Chen Haiou,Ren Gang,Jiang Wei,Guo Xiaoxin,Zhou Juanyu,Yan La,Yan Jinhua,Liu Xingzhu,Yuan Yu,Chen Yi,Chen Haiyang
Intestinal stem cell (ISC) aging diminishes the regenerative capacity of the intestinal epithelia, but effective therapeutic strategies to counteract human ISC aging remain elusive. Here, we find that the synthesis of α-lipoic acid (ALA) is reduced in old human small intestine. Notably, ALA supplementation inhibits ISC aging and decreases the number of atypical Paneth cells in old human intestinal organoids and in old mouse small intestines. Importantly, we discern that the effect of ALA on mitigating ISC aging is contingent upon the presence of Paneth cells. Inhibiting the mTOR pathway in Paneth cells with ALA or rapamycin significantly increases cyclic ADP ribose (cADPR) secretion and decreases Notum secretion, which, in turn, enhances ISC functions. In this work, our findings substantiate the role of ALA in inhibiting human ISC aging and present a potential therapeutic approach for managing age-related human intestinal diseases.
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MOLECULAR PHARMACEUTICS
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2025
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IF 4.5
Jiantao Meng,Chengang Henry Zhou,Lei Yin,Ji-An Chen,Junwei Xi,Chen Chen,Ting Cai,Yue Gui
Accurate dispensing of small-molecule counterions and coformers is a persistent challenge in solid form screening, particularly for beyond-the-Rule-of-5 (bRo5) drug candidates. In this study, we present the broad applicability of ChemBeads, a coated-bead approach, for a diverse range of molecules. By systematically evaluating multiple model systems, we establish that ChemBeads enable precise and automated small-scale solid addition while maintaining flowability, stability, and uniform surface coatings. Importantly, our results confirm that the introduction of glass beads does not alter the solid form outcome, ensuring reliability in the crystallization experiments. The impact of ChemBeads on crystallization kinetics is also studied. This work demonstrates that coated beads can be applied generally to solid form screening, offering a scalable and automation-compatible solution for high-throughput pharmaceutical development.
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ANALYTICA CHIMICA ACTA
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2020
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IF 5.977
Xiaofei Han,Jia Chen,Zhan Li,Kaijun Quan,Hongdeng Qiu
A magnetic porous carbon (Fe 3 O 4 @PC) was successfully fabricated based on combustion combined with solvothermal method , and then used as magnetic solid-phase extraction absorbent for the determination of four triazole fungicides . The porous carbon was fabricated by imperfect combustion of filter paper loaded with zinc nitrate hexahydrate, which possessed extremely abundant pores, high specific surface area (908.05 m 2 g −1 ) and large pore volume . Due to the introduction of solvothermal method used to prepare Fe 3 O 4 @PC, homogeneously distributed magnetic nanoparticles and high saturation magnetization were obtained. Compared with another magnetic porous carbon (Fe 3 O 4 @C), Fe 3 O 4 @PC obviously enhanced enrichment factors and extraction recoveries. Several key parameters influencing extraction efficiency were optimized. The satisfactory enrichment factors, low limits of detection of the method and good linearities were achieved under the optimal conditions. The relative recoveries ranged from 82.8% to 113.2% in three spiked real samples with relative standard deviations lower than 6.2%. The results indicated the great potential of the novel Fe 3 O 4 @PC as adsorbent for the extraction of triazole fungicides from complex real samples.
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BIOORGANIC CHEMISTRY
·
2025
·
IF 4.7
Wenhao Zhou,Yijie Cai,Xilei Wang,Yijun Tu,Jiejuan Jiang,Jianqing Yu
Alantolactone (AL) and isoalantolactone (IAL) are the bioactive components of Inula racemosa Hook. f. and constitute a significant portion in this herb. These two compounds are widely utilized in pharmaceuticals, cosmetics, agriculture and other fields due to their extensive biological activities, exhibiting remarkable market potential. However, their current acquirement remains primarily reliant on traditional Chinese medicine, which makes it necessary to optimize the extraction process. Additionally, the minor components, particularly sesquiterpenes, are often overlooked due to the high contents of AL and IAL, which makes their chemical components still unclear. This study developed an HPLC detection method and optimized an ultrasound-assisted extraction process with response surface methodology (RSM), achieving optimal parameters: liquid-solid ratio of 15.34: 1, 88.92 % ethanol, and 49.21 °C. Furthermore, to identify the minor components, a novel combination of Feature-based Molecular Networking (FBMN), Network Annotation Propagation (NAP), and ClassyFire was employed. The results revealed that the minor sesquiterpenes still accounted for a high proportion. Systematic separation yielded 22 sesquiterpenes, including three novel compounds ( 1 – 3 ) and 19 known ones ( 4 – 22 ). Biological evaluation demonstrated that some compounds exhibited stronger cytotoxicity than AL and IAL against HepG2, SKOV3 and HeLa cells, and compound 14 showed the best cytotoxicity via apoptosis induction. Moreover, four compounds exhibited synergistic effects with cisplatin (CDDP) on SKOV3 cells. Compounds 14 and 15 displayed potent anti-inflammatory effects with IC 50 < 3 μM. These findings indicated that the neglected part still contain bioactive sesquiterpenes, deserving for further exploration.
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International Journal of Nanomedicine
·
2025
·
IF 6.5
Qiao Zeng,Jie Chen,Han Zhang,Wenying Yu,Haonan Xu,Qiao Wang,Zhan Tang
Purpose To develop everolimus-loaded nanosuspensions (EV-sus) for the in vitro and in vivo corneal neovascularization (CNV) treatment.Results Everolimus was encapsulated into nanosuspensions using a solvent volatilization technique. The developed nanosuspensions exhibited a drug concentration of 0.96 mg·mL−1, an average particle size of 141.0 ± 1.0 nm, and a zeta potential of −12.2 ± 0.4 mV. C6-labeled EV-sus uptake by Human Corneal Epithelial Cells-Transformed (HCE-T) was time-dependent, energy-dependent, and involved multiple endocytic pathways, including caveolae- and lipid raft-mediated endocytosis, clathrin-mediated endocytosis, and caveolae-mediated endocytosis. The nanosuspensions exhibited efficacy in inhibiting VEGF-induced proliferation, migration, and tube formation in Human Umbilical Vein Endothelial Cells (HUVECs). According to RT-qPCR, the in vivo CNV model showed that EV-sus effectively reduced neovascularization, decreased vascular length and area, and diminished the expression of IL-1, IL-6, MMP-9, VEGF, and TNF-α. Additionally, the rabbit eye irritation test confirmed the safety and tolerability of the formulation.Conclusion These findings indicate that EV-sus might be an effective therapy for corneal neovascularization. The formulation exhibits excellent biocompatibility, efficient cellular uptake, and robust anti-angiogenic activity, suggesting its suitability for ocular administration and the potential to mitigate CNV progression with minimal irritation.
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FREE RADICAL BIOLOGY AND MEDICINE
·
2025
·
IF 8.2
Longyan Yang,Ruili Yin,Ziyu Shan,Anqi Feng,Kun Li,Yan Wang,Ke Yu,Yongsong Xu,Lin Mao,Jianan Lang,Baoyu Zhang,Dong Zhao
Aims Overweight and obesity are closely associated with hyperuricemia (HUA). However, the effect of obesity-induced adipokine on the level of serum uric acid (UA) has not been fully elucidated. This study aimed to determine the role of adipokine in the pathogenesis of HUA. Methods Omental adipose tissues from HUA patients with obesity were collected for data- independent acquisition (DIA) proteomics analysis, and the secreted protein angiopoietin-like protein (ANGPTL2) was identified and further validated via Western blot and ELISA. Angptl2 knockout (ko) and adipocyte-specific ANGPTL2 overexpression mice were generated to establish HUA models. HK2 cells and primary renal tubule epithelial cells (RTECs) were applied to induce HUA cell model and treated with recombinant human ANGPTL2 or supernatants derived from C3H10 cells differentiated into adipocytes. Result ANGPTL2 levels were significantly elevated in the omental adipose tissue from HUA with obesity patients compared to control participants. Circulating ANGPTL2 levels were also increased, and positively correlated with serum UA levels, especially in male participants. Plasma UA levels were significantly decreased in Angptl2 ko mice, coinciding with up-regulated expression of ATP binding cassette subfamily G member 2 (ABCG2) and down-regulated glucose transporter 9 (GLUT9) in renal tissue. However, plasma UA levels were significantly increased, accompanied by decreased ABCG2 expression and enhanced GLUT9 expression after adipocyte-specific ANGPTL2 overexpression. Furthermore, adipocyte- derived ANGPTL2 increased UA level in cell supernatants through the inhibition of protein kinase B (AKT)/ABCG2 signaling in RTECs and HK2 cells. Conclusion Adipokine ANGPTL2 levels were significantly elevated in HUA patients with obesity. Circulating ANGPTL2 concentrations were independently associated with serum UA levels, particularly in obese males. Adipocyte-secreted ANGPTL2 promoted the level of UA through AKT/ABCG2 signaling in renal tubular cells. These findings establish ANGPTL2 as a critical adipokine linking obesity to hyperuricemia and suggest its potential as a novel therapeutic target for HUA.
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ANALYTICA CHIMICA ACTA
·
2015
·
IF 4.513
Qing Wang,Mao Ye,Li Xu,Zhi-guo Shi
A mixed-mode chromatographic packing material, C18 and diol groups modified silica (C18-Diol), was prepared with controllable hydrophobicity and hydrophilicity . It demonstrated excellent aqueous compatibility and stability in aqueous mobile phase ; compared to the traditional C18 column, improved peak shape of basic analytes was also obtained. Additionally, it exhibited both reversed-phase liquid chromatographic (RPLC) and hydrophilic interaction chromatographic (HILIC) performance; the analyte separation scope was thus enlarged, demonstrated by simultaneous separation of twenty acids, bases and neutrals. More interestingly, a novel on-line two-dimensional liquid chromatography on the single column (2D-LC-1C) was established by modifying the high performance liquid chromatographic instrument only with the addition of an extra six-port two-position valve. The early co-eluted components of the extract of Lonicera japonica on the 1st-dimension (RPLC) were collected for the online re-injection to the 2nd-dimension (HILIC) by conveniently varying the mobile phase components. Six more peaks were obtained. The established system was simple, easy operation and low cost, which had advantages in analyzing complicated samples.
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