MOLECULAR PHARMACEUTICS
·
2025
·
IF 4.5
Yanzhi Wang,Shanshan Sun,Mengqian Liu,Sai Zhang,Jiaxin Zheng,Hongmin Liu
Paclitaxel (PTX) is a widely used chemotherapeutic agent, but its clinical utility is limited by poor solubility, systemic toxicity, and inadequate tumor targeting. To address these challenges, we developed a novel glycyrrhetinic acid–biguanide conjugate (GABG) capable of forming self-assembling, carrier-free nanoparticles. GABG’s amphiphilic and self-emulsifying properties enable efficient PTX encapsulation and targeted delivery. PTX-loaded GABG nanoparticles (PTX@GABG NPs) significantly enhanced cytotoxicity against multiple tumor cell lines, improving cellular uptake and selective tumor accumulation. Molecular dynamics simulations confirmed stable PTX–GABG interactions, supporting the structural integrity of the nanocomplex. In vivo biodistribution studies revealed strong liver tropism following intraperitoneal administration, with tumor-targeting efficiency comparable to intravenous delivery. The cellular uptake of GABG nanoparticles in H22 cells was shown to be governed by GA receptor-mediated endocytosis, with both caveolae- and clathrin-dependent pathways contributing to their efficient internalization. Therapeutic evaluations demonstrated that PTX@GABG NPs induced superior tumor inhibition compared to free PTX, driven by enhanced apoptosis and ROS-mediated cytotoxicity. Notably, the antitumor efficacy of intraperitoneal administration was comparable to that of intravenous injection, highlighting its potential as a less invasive yet effective delivery route. Given its dual functionality in drug encapsulation and liver targeting, GABG presents a promising platform for hepatic tumor therapy. Its cationic biguanide groups may further enable encapsulation of biopharmaceuticals such as RNA, underscoring its versatility in precision nanomedicine.
研究领域:
纳米医学
·
药学
·
癌症治疗
·
药物递送
·
分子药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
·
2025
·
IF 3.8
Chen Biqing,Gao Jiayin,Sun Haizhu,Zhao Yinghan,Liu Yan,Lv Xinpeng,Qiu Xiaohong,Li Yang
Chemotherapy remains a cornerstone in the treatment of multiple solid and gynecologic malignancies, including endometrial cancer, ovarian cancer, and breast cancer. Carboplatin, epirubicin, gemcitabine, paclitaxel, topotecan, and docetaxel are widely used in combination regimens; however, there is still a lack of sensitive, rapid, and multiplex technologies for real-time monitoring of chemotherapeutic drug concentrations. In this study, we developed a carboxyl-polyethylene glycol (PEG)-modified magnetite (Fe₃O₄@PEG) nanoplatform combined with artificial intelligence (AI)-driven spectral analysis to achieve ultra-sensitive and multiplex detection of six chemotherapeutic drugs. Fe₃O₄ nanoparticles were synthesized by co-precipitation and subsequently functionalized with carboxyl-PEG to enhance drug capture efficiency and resistance to matrix interference. Using a confocal Raman imaging system, SERS spectra of single and mixed drug systems were collected, and convolutional neural networks (CNNs) were employed for automated feature extraction and classification to enable qualitative and quantitative analysis. The constructed SERS platform achieved 10⁻⁷–10⁻⁸ milligrams per milliliter (mg/mL) detection limits for all six drugs in serum matrices, with classification accuracies exceeding 95% in multiplex mixtures. For improved quantitative accuracy and normalization, the 2078 cm⁻ 1 Raman peak of deuterated methanol (CD₃OD) was employed as an internal standard to correct for potential fluctuations in laser intensity and sample concentration. Within the simulated therapeutic concentration range, quantitative regression yielded R 2 ≥ 0.98. This AI-SERS platform offers advantages of multiplex detection, trace-level sensitivity, and strong anti-matrix interference, holding great promise for pharmacokinetic monitoring and individualized chemotherapy optimization across a broad range of solid tumors. Graphical abstract Schematic illustration of an AI-integrated Fe 3 O 4 @PEG–SERS nanoplatform for multiplex detection of six chemotherapeutic agents (carboplatin, epirubicin, gemcitabine, paclitaxel, topotecan, and docetaxel). Carboxyl-PEG–modified magnetite nanoparticles enhance drug adsorption and stability, while convolutional neural networks enable accurate qualitative and quantitative spectral analysis for personalized chemotherapy optimization.
研究领域:
肿瘤学
·
纳米技术
·
分析化学
·
生物医学工程
·
药学
·
人工智能
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR LIQUIDS
·
2025
·
IF 5.2
Haiyan Yu,Chao Wang,Zhilin Meng,Hongkun Zhao
Cocrystal phase diagram can guide the synthesis of cocrystal using solvent crystallization method. Although the nicotinamide (NTA)-benzoic acid (BA) cocrystal, NTA·BA, has been produced in solvents for several years, no information is available regarding the cocrystal phase equilibrium relevant to the systems. This article takes the NTA·BA cocrystal as the research object, through the isothermal saturation technique, the solubilities were firstly measured comprehensively at 298.15, 308.15, and 318.15 K for the NTA + BA + ethanol/isopropanol/acetone systems. Nine cocrystal phase diagrams were created. Three pure solids were included in each ternary system, which were NTA, BA, and NTA cocrystal with BA (NTA·BA, 1:1, mole ratio). In addition, each ternary system yielded two invariable point, five solid crystalline areas, and three curves of saturation with solutions. In the preferred solvents, the cocrystal exhibits exceptional stability. By examining these cocrystal diagrams, the cocrystal crystallization behavior in solvent was better understood, and the stable cocrystal locations in particular solvents were identified. Subsequently the improved solubility product and solution complexation model was used here to link the mutual solubilities along the crystalline curves of the NTA·BA cocrystal, producing the highest value of relative standard error of 3.69 %. Finally, based on the research of molecular dynamic simulation and quantum chemistry, the hydrogen-bonding and vdW forces are advantageous interactions when forming the NTA·BA cocrystal. The cocrystal phase diagram determined in this contribution could guide the production and separation of the NTA·BA cocrystal in a solvent.
研究领域:
药学
·
材料化学
·
物理化学
·
计算化学
·
晶体工程
✓ 已验证
产品关联
DOI
高影响因子
BIOFOULING
·
2025
·
IF 2
Hui Yuan,Ming Lu,Chen Shi,Chunshuang Li,Ze Yao,Hui Shang,Xiang Li,Heshui Yu,Songtao Bie
Plumbagin, also known as 5-hydroxy-2-methyl-1,4-naphthoquinone (PLB), is a naturally occurring naphthoquinone molecule that has demonstrated strong antibacterial and antibiofilm properties against Staphylococcus aureus (S. aureus). However, the potential of PLB to eradicate mature biofilms and the underlying mechanisms involved remain unclear. In this study explored the effects of PLB on disrupting mature S. aureus biofilms, focusing on its impact on the extracellular polymeric substances (EPS) and potential mechanisms of action. Crystal violet (CV) and XTT assays demonstrated that PLB significantly reduced both the biomass and metabolic activity of mature S. aureus biofilms in a concentration-dependent manner. High-content screening (HCS) imaging demonstrated that PLB treatment induced significant alterations in the biofilm EPS architecture, leading to a substantial reduction in overall biomass and average thickness, with disruption severity correlating positively with PLB concentration. Using molecular fluorescence probing techniques, this study found that treatment with PLB resulted in a marked reduction in EPS components, including extracellular polysaccharides (PIA), proteins, and extracellular DNA (eDNA), compared to untreated controls. Molecular docking analysis revealed that PLB strongly interacts with several key S. aureus proteins involved in EPS production, such as IcaA, IcaD, IcaB, IcaC, Bap, ClfB, and CidA, particularly binding strongly to the active sites of IcaA and Bap. Furthermore, gene expression analysis indicated that PLB downregulated genes associated with biofilm EPS production. Overall, these findings suggest that PLB effectively disrupts S. aureus biofilms by targeting the EPS. These results highlight PLB as a promising candidate for targeting mature S. aureus biofilms in chronic infections.
研究领域:
微生物学
·
抗菌研究
·
生物膜生物学
·
药学
·
分子对接
·
传染病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·10796
·
IF 15.7
Zhou Yue,Li Junhao,Xu Zhongyi,Zhao Yixin,Zhang Shanshan,Liu Tong,Yao Yelan,Fang Lu,Cai Yu,Ye Xuesong,Liang Bo
Real-time in vivo monitoring of levodopa pharmacokinetics is essential to address its narrow therapeutic window in Parkinson’s disease (PD) therapy. However, current methods require excessive sample volumes, suffer low sampling frequencies, and fail to capture complete pharmacokinetic profiles. Here, we present an in vivo monitoring system for real-time tracking of levodopa levels in interstitial fluid (ISF) using a spindle-shaped carbon nanotube (CNT) fiber electrochemical sensor functionalized with a nanoscale molecularly imprinted polymer (nanoMIP) on single electroactive CNTs. The core-shell (CNT-nanoMIP) nanostructures provide sensitive, selective detection of levodopa, along with resistance to both biofouling and chemical fouling in continuous ISF detection. The system was validated for monitoring complete pharmacokinetic profiles and assessing temporal correlations between ISF/plasma levodopa pharmacokinetics in both PD rat models and healthy rats. We also demonstrated optimized and adjustable pharmacokinetic profiles through in vivo experiments with rationally designed levodopa dosing regimens, highlighting the system’s potential for personalized PD pharmacotherapy.
研究领域:
生物医学工程
·
神经科学
·
药学
·
传感器与生物传感器
·
可穿戴与植入式设备
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Science Advances
·
2025
·Vol. 11
·期 47
·
IF 12.5
Ziqi Gao,Huilong Du,Shuyuan Yu,Qi Li,Ruiqi Shi,Zengliang Jiang,Huayong Yang,Luqi Shen,Hongzhao Zhou
The small intestine’s intricate structure enables vital functions such as nutrient absorption, microbial defense, and barrier protection, yet replicating its complexity in vitro remains a substantial challenge. We engineered a three-dimensional bioprinted intestinal model featuring biomimetic circular folds and zonated shear stress distribution to recapitulate native physiology. A filament-resolved embedded bioprinting approach enabled high-fidelity fabrication of thin-walled, continuous structures that shaped physiologically relevant flow microenvironments essential for epithelial development. These shear stress patterns regulated tight junctions, secretory activity, and transporter expression, driving region-specific epithelial specialization into barrier or absorptive phenotypes. Coculture with probiotic Lactobacillus plantarum activated localized immune responses and modulated epithelial function through spatially distinct colonization. Regional flow differences governed the transport of nutrient and drug probes via transcellular and paracellular pathways. Quantitative assessment of drug absorption demonstrated strong in vitro–in vivo correlation, validating physiological relevance. By unifying structural, mechanical, and functional complexity, this platform advances intestinal models for studying physiology, host-microbe interactions, and drug transport.
研究领域:
组织工程
·
生物医学工程
·
微生物学
·
药学
·
生理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Jianxin Li,Yingchen Ni,Yanjie Tao,Hao Cai,Anqi Wu,Fengyuan Zhang,Shijie Meng,Yuyang Luo,Weidong Zhang,Youhua Wang
Rheumatoid arthritis (RA) is a chronic autoimmune disorder marked by progressive joint degradation, with mitochondrial dysfunction significantly contributing to its pathogenesis. Despite extensive research into therapeutic strategies, successfully addressing mitochondrial dysfunction in RA poses a significant challenge. This paper presents an innovative functionalization method, deploying hydrocaffeic acid-modified chitosan, in conjunction with the selective calcium chelator ethylene glycol bis(β-aminoethyl ether)-N,N,N’,N’-tetraacetic acid (EGTA), and incorporating stromal cell-derived factor 1 alpha (SDF-1α). In vitro , this functionalized hydrogel exhibited a significant decrease in intracellular reactive oxygen species (ROS) levels, stabilization of mitochondrial membrane potential, mitigation of calcium overload, inhibition of mitochondrial dysfunction-induced cellular senescence, and a reduction in the release of senescence-associated secretory phenotype components. In vivo , this hydrogel effectively modulated immune responses and aided cartilage repair in a collagen-induced arthritis rat model. From a mechanistic perspective, high-throughput sequencing suggests that the therapeutic efficacy of this hydrogel may be associated with its ability to modulate mitochondrial function and inflammatory pathways. In summary, the hydrocaffeic acid- and EGTA-based functionalization strategy provides an innovative and straightforward process for integrating multiple functionalities into a single delivery platform, demonstrating the potential for tissue regeneration applications extending beyond RA.
研究领域:
生物医学工程
·
风湿病学
·
免疫学
·
组织工程
·
药学
·
线粒体生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Hongyu Zhang,Guoshun Lin,Yifei Wang,Aihui Zheng,Hanlin Luo,Zhang Cao,Guige Hou,Yun Hou
Background Bisphenol S (BPS) is widely used in consumer products and food packaging, but its safety and potential risks have garnered increasing attention. Hydroxytyrosol (HT), a natural polyphenolic compound with potent antioxidant and anti-inflammatory activities, is yet to be investigated for its potential to reverse BPS-induced effects and the underlying mechanistic pathways. Methods The toxicological potential of BPS was assessed using the computational platform ProTox 3.0. Molecular experiments were performed to elucidate the effects of BPS on the nervous system. Protein-protein interaction networks were constructed to predict the targets of BPS. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were used to explore the potential mechanisms of action, followed by molecular docking studies. We examined the therapeutic efficacy of HT against BPS-induced nerve damage using molecular assays and in vivo murine models. The key target identified by molecular docking was validated using RT-qPCR. Results Significant neurotoxic effects of BPS were identified using platform-based predictive analysis. The experimental results demonstrated that exposure to BPS not only reduced the viability of BV2 and HMC3 microglial and elevated intracellular reactive oxygen species (ROS) levels, but also induced a phenotypic shift in microglia toward a pro-inflammatory state, thereby may underscore its neurotoxic effects. Based on the results of the network toxicology analysis, BPS is potentially capable of exacerbating nerve damage via its modulatory effects, such as its modulation of cytochrome P450 Family 1 Subfamily A (CYP1A), like-CYP1A1, CYP1A2, and cytochrome P450 Family 2 Subfamily B6 (CYP2B6), etc. Finally, subsequent confirmation using network pharmacology and molecular docking analysis revealed that HT is capable of counteracting BPS-induced effects, and that CYP1A1 is highly likely to be a pivotal target implicated in both BPS-mediated toxicity in microglia and the therapeutic mechanisms of HT. This was further verified using RT-qPCR. Conclusion CYP1A1 is a critical mediator of BPS-induced toxicity and a potential therapeutic target of HT. These findings highlight the potential of natural compounds to mitigate environmental toxicant-induced neurological damage.
研究领域:
毒理学
·
神经药理学
·
环境健康
·
分子生物学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF THERMAL ANALYSIS AND CALORIMETRY
·
2025
·
IF 3.1
Wu Chuan Chao,Ye You Wen,Cheng Zhao Yang,Li Yu qi,Liu Yan,Wu Hai Xia,Wu Jian Rong,Liu Qing Tao,Huang Yi Na
Polydatin (PD) possesses a variety of pharmacological activities, but its poor aqueous solubility, stability, and bioavailability limit its application. To improve PD’s water solubility, PD/β-CD inclusion complexes were prepared by solution stirring method and characterized by infrared spectroscopy, X-ray diffraction spectroscopy, nuclear magnetic resonance hydrogen spectroscopy, and molecular docking. The results showed that PD and β-CD successfully generated an inclusion complex with a 1:1 host–guest ratio and a stabilization constant of 4362 M −1 . To further explore the beneficial potential, the antioxidant capacity of PD/β-CD after digestion and the pattern of change during digestion were evaluated in stages by simulated digestion and simulated fermentation in vitro. The simulated digestion process hardly changed the total sugar and reducing sugar contents ( P > 0.05). During the simulated fermentation process, the pH value kept decreasing, and the short-chain fatty acid content in the fermentation products increased significantly ( P < 0.05), with the acetic acid content showing the highest increment (1.90 ± 0.35 g L −1 ). In addition, at the phylum level, PD/β-CD inclusion significantly increased the relative abundance of Firmicutes and Actinomycetes and significantly decreased the relative abundance of Proteobacteria , relative to the β-CD group. At the genus level, beneficial bacteria such as Bifidobacterium and Lactobacillus proliferated in the PD/β-CD group, and the relative abundance of potentially pathogenic bacteria such as Streptococcus , and Escherichia-Shigella was significantly reduced. The experimental results indicated that PD/β-CD inclusion complexes were a potential prebiotic with high potential in the field of medicine and health care.
研究领域:
药学
·
营养生物化学
·
微生物学
·
药物递送系统
✓ 已验证
产品关联
DOI
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
·
2025
·
IF 4.6
Ran Duan,Hanlin Guo,Zhengxiong Peng,Xinyu Yu,Juping Yu,Hong Tian,Wei Liu
PTC124 (Ataluren) is a small molecule drug for the treatment of genetic diseases that has been shown to promote early termination codon read-through. In this study, the binding model of PTC124 to human serum albumin and eukaryotic stop codon recognition factor (eRF1) was established in vitro . In the cell model, the read-through effect of PTC124 on the stop codon was confirmed. Fluorescence analysis showed that PTC124 could spontaneously bind eRF1 and HSA, the binding constants were 3.132 ± 0.643 × 10 4 and 2.963 ± 0.218 × 10 5 L/mol (298 K), respectively. Thermodynamic analysis indicated that the binding to eRF1 was driven mainly by hydrophobic interactions, hydrogen bonding, and van der Waals forces, whereas the binding to HSA was driven primarily by hydrogen bonding and van der Waals forces. Structural analysis revealed perturbations in the secondary structure of both HSA and eRF1 induced by PTC124, while the overall native folds of the proteins were maintained. In addition, a binding model of the interaction between PTC124 and eRF1/HSA was established by molecular simulation and STD-NMR. The binding model described in this paper explains the interaction mechanism between PTC124 and its utility and transport targets at the molecular level, which is helpful for the design and synthesis of new molecules related to PTC124 structure and based on its mechanism of action.
研究领域:
药学
·
分子生物学
·
生物化学
·
结构生物学
·
遗传性疾病
·
药物设计
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
·
2025
·
IF 4.9
Hua Nie,Xiao-Min Liu,Sheng-Yuan Zhang,Qi-Xuan Yang,Huang Zeng,Xiao-Dong Luo,Jiun-Long Yang
This study optimized polyethylene glycol (PEG) chain length in cholesterol-GalNAc conjugates (CHS-PEG n -6-GalNAc, n = 2–5) to enhance hepatic targeting of liposomes by balancing glycan exposure and glycocluster conformation. The conjugates were synthesized via enzymatic catalysis and incorporated into liposomes (LP-PEG n -6-GalNAc). Systems were evaluated through in vitro HepG2 cell uptake, in vivo murine biodistribution, and molecular dynamics (MD) simulations. LP-PEG n -6-GalNAc showed significantly higher in vitro uptake ( P < 0.01 vs unmodified liposomes) and superior in vivo hepatic accumulation ( P < 0.01). ASGPR-mediated targeting was confirmed by competitive inhibition (GalNAc in vitro , asialofetuin in vivo ; both P < 0.01). Targeting efficiency exhibited identical PEG-length dependency: PEG 3 > PEG 4 > PEG 5 > PEG 2 . MD simulations revealed a dual mechanism: Shorter chains (PEG 2 ) maintained higher glycocluster stability (frequency = 40.8 %; RMSF = 0.39 Å) but limited GalNAc accessibility (SASA = 49.9 %). Longer chains (PEG 4-5 ) increased SASA (73.38–86.08 %) but reduced stability (frequency = 23.0–35.0 %; RMSF = 1.05–1.30 Å). PEG 3 balanced SASA (61.7 %) and stability (36.2 %), synergistically enhancing uptake. This provides the first evidence that PEG length coordinates glycan accessibility and glycocluster stability to improve hepatic targeting.
研究领域:
药物递送
·
纳米医学
·
分子靶向
·
糖化学
·
药学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF MOLECULAR STRUCTURE
·
2025
·
IF 4.7
Xin Jiang,Siyu Yuan,Jie Yang,Hui Liao,Hansong Wu,Baolin Jiang,Kun Qian
Drug cocrystal can not only improve the physicochemical properties of drugs but also exert a synergistic effect without altering the original structure of drugs. Herein, we successfully synthesized a norfloxacin-kaempferol cocrystal hydrate (cocrystal 1 ) from an antibacterial drug and a flavonoid active ingredient. Compared with norfloxacin or kaempferol alone, cocrystal 1 enhanced antibacterial activity against Gram-positive bacteria ( S. aureus ), Gram-negative bacteria ( K. pneumoniae and P. aeruginosa ), and fungus ( C. albicans ). Meanwhile, cocrystal 1 enhanced the antioxidant activity of kaempferol and also improved the solubility of norfloxacin and kaempferol. Moreover, cocrystal 1 enhanced the anticancer activity against human breast cancer cells MDA-MB-231, colon cancer cells SW480 and lung cancer cells H1299.
研究领域:
药学
·
药物化学
·
晶体工程
·
抗菌研究
·
癌症药理学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）