MONATSHEFTE FUR CHEMIE
·
2014
·Vol. 146
·期 3
·441-447
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IF 1.347
Li Longfei,Chen Lin,Liu Weifeng,Yang Yongzhen,Liu Xuguang,Chen Yongkang
5-Fluorouracil surface-imprinted thermosensitive magnetic microspheres were prepared by using Fe 3 O 4 -encapsulating carbon microspheres as cores, N -isopropylacrylamide as thermosentitive monomer, ammonium persulfate as initiator, N , N ′-methylenebisacrylamide as crosslinker, and 5-fluorouracil as template molecule. The formation of these hybrid microspheres was verified by field emission scanning electron microscopy, transmission electron microscopy, Fourier transformation infrared spectroscopy, thermogravimetry, and dynamic light scattering. The results of the latter measurements show that the as-synthesized microspheres have a hydrodynamic diameter of 326 nm with the lower critical solution temperature of around 43 °C. The obtained microspheres are magnetic and show good potential for controlled loading and release of 5-fluorouracil. Graphical abstract
研究领域:
药剂学
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纳米医学
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肿瘤治疗
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高分子材料科学
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靶向给药系统
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高影响因子
JOURNAL OF LIPOSOME RESEARCH
·
2025
·
IF 4.3
Han Chen,Jin Su,Wenhui Cheng,Linwen Wen,Meiqi Huang,Xuejiao Li,Wei Cai,Qian Ning,Liangjun Guan
5-Fluorouracil (5-Fu) is a chemotherapy drug that can treat various cancers. However, its short plasma half-life and severe adverse reactions limit its wide application in clinical utility. To overcome these drawbacks, in this study, 5-Fu long-circulating liposomes (SSL-5-Fu Lip) were prepared by the film hydration method. DSPE-PEG2000-FA was conjugated to the surface of SSL-5-Fu Lip through amidation reaction, resulting in the successful preparation of FA-SSL-5-Fu Lip. The particle size and zeta potential were measured. The encapsulation efficiency of 5-Fu was determined by high-performance liquid chromatography (HPLC), and the drug loading was calculated. The stability of FA-SSL-5-Fu Lip was evaluated at 4 °C based on particle size and PDI. Pharmacokinetic studies were conducted in male Sprague-Dawley (SD) rats. The average particle size of the liposomes was 139.11 ± 3.1 nm, and the zeta potential was −4.30 ± 0.91 mV. The encapsulation efficiency and drug loading of 5-Fu were 76.88 ± 4.23% and 24.14 ± 0.97%, respectively. The half-lives of 5-Fu and FA-SSL-5-Fu Lip were 0.319 h and 1.059 h, respectively. It can be preliminarily proved that FA-SSL-5-Fu Lip has the effect of prolonging circulation time. Compared with free 5-Fu, it prolongs the circulation time of the drug in the body, laying a foundation for its clinical application.
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MOLECULAR DIVERSITY
·
2026
·
IF 4.3
Zhang Ran,Tang Liqing,He Jianglong,Jiang Guanyu,Su Yingfei,Jiang Xueping,Wu Ping,Zhang Dongyang,Chen Sitong,Li Hao,Gui Zhongzheng
As FDA-approved chemotherapeutic agents, paclitaxel (PTX) and 5-fluorouracil (5-FU) are widely used in the clinic but suffer from dose-limiting toxicities. To overcome these limitations, we designed and synthesized two novel 5-FU prodrugs conjugated with the microtubule inhibitor PTX. The hybrids exhibited potent cytotoxicity against cancer cell lines while demonstrating favorable selectivity over normal human cells, outperforming the individual agents or their combinations. As a representative, FP2 potently induced DNA damage through downregulation of thymidylate synthase (TS), arrested the cell cycle at S-phase, and suppressed metastasis of HCT-116 cells. Moreover, FP2 triggered mitochondrial dysfunction, characterized by loss of mitochondrial membrane potential, increased ROS generation, downregulation of Bcl-2, and upregulation of Bax. FP2 also triggered oxidative stress, elevating MDA and NO levels, depleting GSH and SOD, downregulating Nrf2, and upregulating HO-1. Additionally, FP2 activated the PERK/ATF4/CHOP signaling pathway, leading to endoplasmic reticulum (ER) stress. Furthermore, FP2 induced autophagic cell death, as evidenced by the formation of autophagosomes, an increased LC3 and decreased p62 expression. Collectively, these findings established FP2 as a novel compound with a promising in vitro anticancer profile that promotes HCT-116 cell death through an integrated mechanism involving DNA damage, mitochondrial dysfunction, ER stress, oxidative stress, and autophagy.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2026
·
IF 8.7
Xiaoyan Liu,Yang Li,Changjing Qiu,Zhongming Liu,Shoujuan Wang,Fangong Kong
Conventional drug delivery systems often face challenges such as low biocompatibility, and limited effectiveness; thus, developing sustainable, pH-responsive materials like carboxylated cellulose nanofibrils (CNF) can enhance drug delivery efficacy. In this study, carboxylated CNF was used as raw materials, acrylic acid (AA) was used as a pH-responsive monomer, and a pH-responsive CNF composite aerogel was constructed as a drug carrier using free radical polymerization and physical blending. The microstructure and physicochemical properties of the CNF composite aerogels before and after drug loading were analyzed using advanced technologies including Fourier-transform infrared (FTIR), thermogravimetric analysis (TGA), x-ray diffraction (XRD), elemental analysis, scanning electron microscopy (SEM), and pore size analysis. The introduction of graphene oxide (GO) modified and optimized the network structure of cellulose aerogels and increased the drug-loading capacity. The network structure formed by AA polymerization made the network structure of the CNF composite aerogel more compact and uniform and prolonged the drug-release time. The loading capacities of the CNF-GO-5-FU, CNF-AA-5-FU, and CNF-AA-GO-5-FU CNF composite aerogels for fluorouracil were 286.78, 275.35, and 312.64 mg/g, respectively. The release curve of the CNF composite aerogel demonstrated a pH response that conformed to the first-order kinetics, Higuchi, and Korsmyer–Peppas models. The sustained-release mechanism of the CNF composite aerogel followed the Fickian diffusion mechanism, highlighting the aerogel's strong biomedical application potential.
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MICROCHEMICAL JOURNAL
·
2026
·
IF 5.1
Sai-Nan Qin,Yi-Xue Zhang,Yi-Jie Cao,Ting Wan,Yi-Yang Zhou,Shan-Shan Su,Yu-Qiong Guo,Jian-Jun Sun,Kalle Salminen
Cisplatin (DDP), as a broad-spectrum anticancer drug, requires dynamic monitoring of its blood concentration and intervention in its dosage administration to balance efficacy and safety due to significant individual differences in its metabolism, side effects, and resistance in different patients. However, rapid and robust methods for monitoring and quantifying DDP in complex biological fluids are still lacking. This work presents an electrochemical aptamer-based ( E -AB) sensor for rapid measurement of DDP concentration in blood. In which capture probe aptamers were designed constructed by visualizing and analyzing their binding pockets, followed by molecular docking and circular dichroism to screen the aptamer Apt25, which has a small binding energy and a large conformational change, for use in the construction of the sensor. In the presence of DDP, the aptamer undergoes a conformational change at the electrode interface, altering the electron transfer rate of the electroactive label to detect DDP concentration variations. After systematically using electrochemical techniques to optimize the sensor testing conditions, the sensor can directly analyze and detect DDP in urine and blood with a measurement range of 0.001–2 mM and a detection limit of 1 μM, which satisfies the needs of clinical testing. The spiked recoveries in different biological samples were 80.8–110% and 79–115.2%, respectively. In addition, the sensor has sufficient selectivity and stability, which is expected to enable real-time monitoring of DDP concentration for dosage adjustment and improvement of drug bioavailability at the clinical site.
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NATURAL PRODUCT RESEARCH
·
2026
·
IF 1.6
Di Zhang,Yujiang Dai,Xin Wang,Qi Mai,Lu Jiang,Tuanjie Wang,Huifang Li,Xing Ren,Rongbin Wei
The halophyte Suaeda maritima subsp. salsa (L.) Soó has been utilised as a traditional medicinal herb in China. Its phytochemical profile remains inadequately elucidated to date. In this study, twelve compounds, including one previously undescribed biflavonoid, 3′-methoxy-4′,4′″,5,5″-tetrahydroxy-[C7-O-C7″]-biflavone (1), and eleven known compounds (2∼12), were isolated from the whole plant of S. salsa. Their structures were fully determined via NMR, MS data analysis and literature comparison. The anti-microbial assay revealed that compounds 1, 9, and 12 exhibited an inhibitory effect against P. aeruginosa with an MIC of 25 μg/mL. Additionally, compounds 3, 5, 7, 9 and 12 displayed potent inhibitory activity against the growth of E. coli, with their MIC values ranging from 12.5 to 25 μg/mL. Furthermore, compound 1 showed the cytotoxic activity against human SGC-7901 cells with an IC50 of 89.04 ± 0.26 μm. Biflavonoid 1 represents the first reported occurrence of this class of compounds within the genus Suaeda.
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CHEMISTRY & BIODIVERSITY
·
2026
·Vol. 23
·期 3
·e03369
·
IF 2.9
Xiaoliang Zhao,Lixia Xiong,Haidong Wen,Yuanyuan Ma,Yuxin Wang,Cunjin Wang,Pengcheng Shao,Jing Zhang,Yuhui Zhao,Ji Zhang,Weijie Zhang
The extraction methods significantly affect the yield and structure of polysaccharides. Based on single-factor experiments, response surface methodology optimized ultrasound-assisted extraction conditions for corn silk polysaccharides (CSP): liquid-to-solid 43 mL/g, extraction time 3 h, and ultrasonic power 640 W, yielding 5.83% CSP. Sulfated, phosphorylated, and selenylated derivatives (CSP-S, CSP-P, and CSP-Se) were prepared with substitution degrees of 0.6 and 0.4, and selenium content of 5.3%, respectively. After confirming structures by UV, FT-IR, SEM, monosaccharide, and Congo-red analyses, the bioactivities of the modified CSP were compared. All derivatives improved antioxidant capacity in vitro: phosphorylation boosted DPPH scavenging, while sulfation enhanced hydroxyl and superoxide anion radical elimination. Selenylation markedly inhibited the activities of α-amylase and lipase, and promoted glucose consumption in HepG2 cells, demonstrating hypoglycemic potential. Moreover, all polysaccharides enhanced RAW264.7 cell viability, phagocytosis, and nitric oxide (NO) release, with CSP-S being most effective. Chemical modifications markedly improved CSP bioactivities, highlighting their application prospects. Graphical
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Bio-Design and Manufacturing
·
2026
·
IF 7.9
Xiong Shuyan,Zhao Yong,Cheng Xi,Zeng Lingxiu,Wang Yuwen,Zhou Ying,Bai Xiaoqiao,Wang Jibo,Hu Jie,Liu Yunnan,Cao Hanwen,Zhou Chunyang,Li Changyong,Liu Jing,Chen Pu
Patient-derived colorectal cancer organoids (CRCOs) are increasingly recognized for their ability to preserve genetic, transcriptional, histological, and drug-responsive features of the original colorectal tumors, offering promise in precision medicine and drug development. While the conventional Matrigel dome culture (DOME) approach has been instrumental in enabling valuable investigations, it has limitations—most notably considerable variation in organoid size and drug sensitivity profiles. In this study, we developed an organoid-on-a-chip (CHIP) for forming uniform organoids and improving precision drug evaluation. Specifically, we fabricated the CHIP using three-dimensional (3D)-printing and micro-molding techniques. Using this CHIP, 19 uniform CRCOs can be generated concurrently in a single well of a 96-well plate within three days, each forming from a minimal seeding density of only 100 cells. Furthermore, the CHIP facilitates in situ imaging and continuous monitoring of individual organoids, supporting label-free, morphometric analysis-based drug screening. Organoids cultured on the CHIP show significantly improved consistency, uniformity, and reproducibility over the DOME method. Our CHIP organoids are functionally identical to conventional DOME organoids, but exhibit greater reliability in drug screening. These results support the CHIP’s potential for high-throughput assays and predictive drug screening models.
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Microorganisms
·
2026
·Vol. 14
·期 8
·1859
·
IF 4.7
Yu Lin,Wei Liang,Bo Yu,Lan Ma,Lin Shu,Zhiqun Liang,Wei Zeng
Microbial melanins are natural pigments with broad application potential, andAureobasidium melanogenumis a promising strain for industrial production of melanin. However, the separation, purification, and biological activities of melanin derived from this strain remain largely unexplored. In this study, an efficient extraction and purification process for melanin from the fermentation broth ofA. melanogenumGXZ-6 was established through single-factor optimization, and the final purity of the melanin reached 94.4%. Spectroscopic stability tests showed that the melanin was highly stable under dark, natural light, a wide pH range (2–12), and temperatures ≤ 37 °C. However, UV light, high temperature (>50 °C), ultrasonication, and certain metal ions (especially Cr3+) markedly altered its absorbance at 225 nm. More importantly, the purified melanin exhibited concentration-dependent antiproliferative activity against human cancer cell lines of A549, HCT116, MCF-7, and HepG2, with IC50values ranging from 25.50 to 72.33 μg/mL. HepG2 cells were the most sensitive (IC50= 25.50 μg/mL), and the melanin showed moderate selectivity toward normal hepatocytes (LO2). Mechanistic studies revealed that melanin effectively inhibited HepG2 cell migration, induced apoptosis, depolarized the mitochondrial membrane potential, and activated the caspase-3/PARP pathway. In summary, this study provides a simple, scalable, and environmentally friendly process for producing high-purity melanin with potential antitumor activity.
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高影响因子
PHYTOMEDICINE
·
2026
·
IF 11.3
Jing-Yu Feng,Jing-Ling Yang,Rui Zhang,Kiran Thakur,Jian-Guo Zhang,Jianbo Xiao,Zhao-Jun Wei
DT-13 potently inhibits CRC metastasis with a favorable biosafety profile. • Plectin (PLEC) is identified as the direct intracellular binding target of DT-13. • DT-13 occupies the PLEC CH domain to physically disrupt the PLEC-TPM4 interactome. • Target engagement down-regulate TPM4 and suppresses Akt/ERK-driven EMT programs. Background Metastasis is the leading cause of colorectal cancer (CRC) mortality. Standard 5-fluorouracil (5-FU) has limited anti-metastatic efficacy and dose-dependent toxicities, underscoring the need for therapeutic alternatives with improved safety profiles. Methods This study investigated the anti‑metastatic mechanism of Liriope muscari baily saponins C (DT‑13) in CRC. Cell viability, migration, and invasion were assessed in HCT116 cells. An orthotopic CRC model was established in BALB/c nude mice to compare the therapeutic efficacy and hematological safety of DT-13 against 5-FU. Direct targets of DT-13 were identified using chemical proteomics (small‑molecule pull‑down, cellular thermal shift assay, drug affinity responsive target stability assay) and molecular dynamics simulations. Results DT-13 inhibited HCT116 proliferation (IC 50 ∼19 μM) and reduced migration and invasion by 78% and 90% in vitro. In vivo , DT-13 achieved a comparable reduction in tumor volume to 5-FU (21% of control volume), while exhibiting a favorable safety profile. Chemical proteomics identified plectin (PLEC) as a primary direct target of DT-13. Molecular docking revealed a binding affinity of –7.654 kcal/mol. Mechanistically, DT-13 occupied the calponin homology domain of PLEC, disrupting its interaction with tropomyosin-4 (TPM4). This led to TPM4 downregulation and subsequently inhibition of Akt and ERK signaling pathways, thereby suppressing the epithelial-mesenchymal transition process. Conclusion DT‑13 exerts anti-metastatic effects in CRC by disrupting the PLEC/TPM4 cytoskeletal scaffold. DT-13 achieved potent anti-metastatic efficacy with a significantly improved systemic safety profile compared to 5-FU. These findings highlight the clinical potential of DT-13 as a safer therapeutic alternative for patients with metastatic CRC. Download: Download high-res image (126KB) Download: Download full-size image
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APOPTOSIS
·
2026
·Vol. 31
·期 9
·210
·
IF 9
Xie Jingyi,Wang Simeng,Liu Juan,Zhang Yan,Zhu Haixiao,Cui Rongrong,Yao Yao,Yu Wei,Hou Peng
KRAS mutations are among the most common genetic alterations in colorectal cancer (CRC) and are strongly linked to poor prognosis and therapeutic resistance. However, current treatments targeting KRAS-mutated CRC have shown limited clinical efficacy. Argonaute 2 (AGO2) is a critical component in microRNA (miRNA)-mediated gene silencing complex, which is involved in the maturation of miRNAs and the regulation of target genes. It has been reported that mutated KRAS can interact with AGO2 and impair its function, thereby amplifying the oncogenic potency of mutant KRAS and accelerating tumor progression. To explore the therapeutic implications of this interaction, we developed a peptide inhibitor and engineered peptide-gold nanoparticles (Au-pep) that specifically disrupted KRAS-AGO2 interaction, which dramatically attenuated the malignant phenotype of KRAS-mutated CRC cells. Mechanistically, Au-pep-mediated disruption of the KRAS-AGO2 complex led to partial restoration of the miRNA expression landscape, with let‑7c‑5p emerging as the most significantly up‑regulated effector. As a result, restored let-7c-5p caused a significant down-regulation of key oncogenic drivers (KRAS, c-Myc and Bcl2) to suppress the growth of KRAS-mutated CRC cells and induce their apoptosis. Furthermore, this miRNA restoration conferred dual therapeutic benefits by sensitizing KRAS-mutated CRC cells to 5-fluorouracil (5-FU) via ABCC5 repression and augmenting immunotherapy responsiveness via PD-L1 down-regulation. Our findings, taken together, delineate a new therapeutic paradigm with significant translational potential for improving clinical outcomes in this recalcitrant patient population.
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高影响因子
Chemical Biology & Drug Design
·
2025
·Vol. 105
·期 6
·e70115
·
IF 3.3
Si-qi Zhang,Si-mei Liu,Zi-long Chen,Ke Guo,Xin-xin Yang,Li-hua Zhang,Ya-feng Yan,Ting-ting Zhang,Peng Zhao
This research extracted and purified polysaccharides from Corydalis yanhusuo residue. The structure of purified polysaccharides of Corydalis yanhusuo (CYP-1) was characterized by methods such as infrared spectroscopy, nuclear magnetic resonance, and monosaccharide composition analysis. In addition, the purified polysaccharides were subjected to preliminary studies in vitro for antioxidant and antitumor activities. The average molecular weight of CYP-1 was 1.427 × 10³ kDa. FT-IR analysis revealed that CYP-1 displayed characteristic absorption bands typical of polysaccharides. Furthermore, NMR spectroscopy suggested that the sugar residue units of CYP-1 consisted of →1)-α-D-Glcp-(4→, →6)-α-D-Galp-(1→, and α-D-Arap-(1→. In vitro bioactivity experiments revealed that CYP-1 exhibits antioxidant activity and effectively inhibits HepG2 cell proliferation with an IC 50 value of 1.381 mg/mL, suggesting its potential as a natural antioxidant and antitumor agent.
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危险品化学品经营许可证（带存储）