INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2025
·
IF 5.2
Xiaoyu Hu,Jun Liu,Qingrong Wang,Qiongkun Hu,Hao Sun,Shi Wang,Yu Zhao,Liwei Gu,Jianying Shen,Qinghe Zhao,Feng Sui,Hai Ma
Gemcitabine, a chemotherapeutic agent widely approved for treating various cancers, faces significant clinical challenges, including drug resistance and poor tumor selectivity. To address the limitation of inadequate tumor targeting, a peptide chain was developed to specifically bind to colon cancer cells and conjugated to gemcitabine via aldehyde–amine condensation. This study aimed to exploit the oncogenic activity of the multifunctional protein α-Enolase (ENO1). The therapeutic efficacy of gemcitabine conjugated with the ENO1-targeting peptide (GCB-P) was evaluated through in vitro and in vivo experiments. Cytotoxicity assays and protein blotting analyses were performed on cell lines, including NCM-460, HCT116 and SW620. GCB-P exhibited significantly enhanced selectivity and potency against colon cancer cells compared to gemcitabine alone, with minimal cytotoxicity to normal colorectal cells. In addition, GCB-P demonstrated superior tumor-selective accumulation and release at the tumor site, as evidenced by in vivo metabolic analyses. These findings underscore the potential of GCB-P as an effective colon cancer treatment with reduced off-target toxicity. Furthermore, GCB-P displayed acid-responsive properties, facilitating precise delivery to tumor sites with the aid of homing peptides. These results highlight the promise of ENO1-targeted peptide modification for gemcitabine in developing targeted drug delivery systems for colon cancer.
研究领域:
肿瘤学
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药理学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
Materials Today Bio
·
2025
·
IF 10.2
Qixin Zhao,Shenglu Liu,Tao Bi,Ting Wang,Lei Chen,Juan Huang,Xuemei Yang,Xiyu Dai,Zengjin Liu,Qin Sun
Pancreatic malignancies rank among the most aggressive and fatal carcinomas in modern oncology, presenting significant therapeutic challenges due to their inherent chemoresistance. In the context of our experimental investigations, we have developed a mitochondria-targeted hydrogel formulation, termed SWMU690@PUE, which demonstrates the ability to modulate mitochondrial homeostasis effectively. The hydrogel construct was precisely designed via the spontaneous supramolecular assembly of puerarin (PUE) and SWMU690 components, facilitated under carefully controlled thermodynamic conditions. Comprehensive in vitro analyses of the SWMU690@PUE complex were conducted to rigorously evaluate its efficacy in regulating mitochondrial homeostasis. The experimental findings revealed that SWMU690@PUE exhibited pronounced selectivity for mitochondrial targeting, subsequently diminishing mitochondrial membrane potential—a pivotal parameter in cellular bioenergetics. Our study further demonstrated that SWMU690@PUE effectively mitigates the chemoresistance phenotype associated with mitochondrial dysfunction. This therapeutic potential was exemplified by its capacity to induce mitochondria-mediated apoptotic and ferroptotic cell death, critical oncocidal pathways, in pancreatic carcinoma cells across both in vitro and in vivo models. Additionally, SWMU690@PUE displayed significant antineoplastic activity, as evidenced by its robust inhibition of pancreatic cancer cell proliferation in both experimental frameworks. In conclusion, this study presents an innovative therapeutic approach specifically designed to overcome the persistent challenge of chemoresistance in the treatment of pancreatic neoplasms.
研究领域:
肿瘤学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
MAGNETIC RESONANCE IN CHEMISTRY
·
2017
·Vol. 56
·期 1
·37-45
·
IF 1.601
Chen Yu,Qian Zhang,Peng-yao Xu,Yin Bai,Wen-bin Shen,Bin Di,Meng-xiang Su
Quantitative nuclear magnetic resonance (qNMR) is a well-established technique in quantitative analysis. We presented a validated 1 H-qNMR method for assay of octreotide acetate, a kind of cyclic octopeptide. Deuterium oxide was used to remove the undesired exchangeable peaks, which was referred to as proton exchange, in order to make the quantitative signals isolated in the crowded spectrum of the peptide and ensure precise quantitative analysis. Gemcitabine hydrochloride was chosen as the suitable internal standard. Experimental conditions, including relaxation delay time, the numbers of scans, and pulse angle, were optimized first. Then method validation was carried out in terms of selectivity, stability, linearity, precision, and robustness. The assay result was compared with that by means of high performance liquid chromatography, which is provided by Chinese Pharmacopoeia. The statistical F test, Student's t test, and nonparametric test at 95% confidence level indicate that there was no significant difference between these two methods. qNMR is a simple and accurate quantitative tool with no need for specific corresponding reference standards. It has the potential of the quantitative analysis of other peptide drugs and standardization of the corresponding reference standards.
研究领域:
药物分析
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生物化学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2018
·
IF 3.862
Chenguang Yang,Wantong Song,Dawei Zhang,Haiyang Yu,Lei Yin,Na Shen,Mingxiao Deng,Zhaohui Tang,Jingkai Gu,Xuesi Chen
Gemcitabine is widely used for anticancer therapy. However, its short blood circulation time and poor stability greatly impair its application. To solve this problem, we prepared a poly ( l -glutamic acid)- g -methoxy poly (ethylene glycol)-gemcitabine conjugate ( l -Gem) with a 14.3 wt% drug-loading content. l -Gem showed concentration- and time-dependent cytotoxicity towards 4T1, LLC, MIA PaCa-2 and A2780 in vitro . Pharmacokinetic and biodistribution studies indicated that l -Gem had remarkably enhanced blood stability, prolonged blood circulation time and greatly improved selective tumor distribution compared with free gemcitabine. The area under the concentration–time curve from zero to infinity [AUC (0–∞) ] of l -Gem in plasma was 43-fold higher than that of free gemcitabine. The AUC (0–∞) of the inactive metabolite, 2′-deoxy-2′,2′-difluorouridine in the l -Gem group was ∼20% of that observed in the free gemcitabine group. The drug tumor accumulation ratio in the l -Gem group relative to the free gemcitabine group was 9.9 at 36 h, while the tumor AUC ratio was 15.8. Testing on Balb/C mice bearing the 4T1 tumor further demonstrated that l -Gem had significantly higher anticancer efficacy than free gemcitabine in vivo . These findings indicated that l -Gem has great potential for cancer treatment.
研究领域:
药理学
·
肿瘤学
·
生物材料
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ANALYTICAL AND APPLIED PYROLYSIS
·
2018
·
IF 3.468
Chengjie Wu,Jinzong You,Xuejie Wang
Gemcitabine (GTB) is a nucleoside drug used in chemotherapy for various carcinomas. In order to know why does GTB have good thermal stability, and to further understand the relationship between thermal stability and molecular structure. The thermal decomposition of GTB was measured with various thermal analytical techniques, the gaseous products and the residues of thermal decomposition were determined and identified. The molecular bond orders were calculated. The thermal decomposition mechanism of GTB was discussed. The thermal decomposition kinetics and the prospective lifetime of GTB were studied using the ATSM method. The results indicated that two strong electronegative fluorine atoms on furan ring make the strong charge-transfer (CT) structure to be formed, this strong CT structure remarkably enhance the N-glycosidic bond and the weakest bond, and lead to higher thermal stability and distinctive thermal decomposition mechanism. The thermal decomposition of GTB is a three-stage process. The initial step of decomposition is likely due to the loss of a furan ring. Most of GTB decompose and carbonizes directly to form insoluble substance and small molecules and just part of GTB decompose by way of cytosine stage. The initial decomposition temperature in either nitrogen or air is 235 °C. For decomposition in nitrogen, the apparent activation energy E a and pre-exponential factor A for the initial thermal decomposition are 123.4 kJ mol −1 and 3.80 × 10 10 min −1 , respectively. For decomposition in air, the corresponding E a and A are 126.3 kJ mol −1 and 7.94 × 10 10 min −1 , respectively. GTB has very good thermal stability under routine temperature and dry air atmosphere.
研究领域:
药理学
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药物化学
·
热分析
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产品关联
DOI
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
·
2018
·
IF 2.441
Yilin Sun,Le Zhen,Ying Peng,Jiankun Wang,Fei Fei,Lixiang Aa,Wenjiao Jiang,Xue Pei,Li Lu,Jie Liu,Guangji Wang,Kun Hao
To improve bioavailability and provide resistance to deamination , an array of gemcitabine (dFdC) prodrugs carrying the acyl modifications has been successful in the optimization of pharmacokinetic properties of dFdC, but the reports about 4- N -carbobenzoxy-dFdC (Cbz-dFdC), a dFdC prodrug bearing alkyloxycarbonyl modification, are relatively rare. Notably, in vivo enzymatic hydrolysis was an absolutely essential factor for the activation of these prodrugs, which is correlated with the anti-tumor activity. Therefore, detailed metabolism studies of Cbz-dFdC should be carried out for a more authentic pharmacodynamic evaluation. In order to detect the pharmacokinetic characteristics of Cbz-dFdC, a selective, sensitive and accurate method for the simultaneous determination of Cbz-dFdC, along with dFdC and its major metabolite dFdU in rat plasma was developed and validated using UFLC–MS/MS techniques. Column was at 40 °C for separation using an eluent with acetonitrile and 0.1% formic acid , 1 mM ammonium formate at a flow rate of 0.2 mL/min. Detection was performed using ESI source in positive ion selected reaction monitoring mode by monitoring the following ion transitions m / z 398.1 → 202.2 (Cbz-dFdC), m / z 264.1 → 112.0 (dFdC), m / z 265.3 → 113.2 (dFdU) and m / z 246.1 → 112.0 (IS). Analytes were extracted by simple precipitation with acetonitrile containing internal standards followed by liquid-liquid extraction with ethyl acetate . The calibration curves of Cbz-dFdC, dFdC and dFdU were linear in the concentration range of 2 to 500 ng/mL, 2 to 500 ng/mL and 40 to 10,000 ng/mL, respectively. The assay ranges selected for the three analytes were appropriate and minimized the need for reanalysis. All the validation data, such as intra- and inter-day precision, accuracy, selectivity and stability, were within the required limits. In conclusion, the sensitive analytical assay was selective and accurate for the determination of rat plasma concentrations of Cbz-dFdC, dFdC and dFdU from a single LC–MS/MS analysis and well-suited to support pharmacokinetic studies.
研究领域:
药物化学
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分析化学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2026
·
IF 12.4
Man Lung Lee,Weiwei Jiang,Jack Chun Hin Chen,Wai Wing Cheng,Ellen Ngar-Yun Poon,Hiu Yee Kwan,Hung-Wing Li
Herein, we engineered biodegradable, ROS-responsive polymersomes (HA-PGC) encapsulating gemcitabine (GEM) and copper peroxide nanoparticles (CuO₂), functionalized with hyaluronic acid (HA) to target CD44-overexpressing TNBC cells. Upon reaching the acidic TME, CuO₂ decomposes to generate hydrogen peroxide (H₂O₂) and Cu 2+ ions, triggering robust ROS production via a Cu-based Fenton-like reaction. Elevated ROS simultaneously suppresses cytidine deaminase (CDA), enhancing GEM activation, and depletes glutathione (GSH), reducing ROS scavenging. The induced oxidative stress further promotes immunogenic cell death (ICD), facilitating dendritic cell maturation and enhancing tumor-infiltrating lymphocytes. Consequently, HA-PGC nanoparticles effectively convert cold tumors into hot tumors, significantly improving anti-PD-L1 immunotherapy efficacy. We demonstrated a novel, multifunctional nanoparticle platform combining chemodynamic therapy and immunotherapy, presenting a promising strategy to overcome resistance in triple-negative breast cancer treatment and guide future intelligent immunotherapeutic system design.
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产品关联
DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2016
·
IF 3.902
Jianfeng Wang,Xiaomin Zhang,Yixin Cen,Xianfu Lin,Qi Wu
Gemcitabine is an important pyrimidine antimetabolite that inhibits cellular DNA synthesis. However, the therapeutic efficacy and clinical benefit of gemcitabine are severely compromised due to its rapid plasma metabolism and low selectivity towards tumor tissues. To overcome these limitations, we prepared novel PEGylated gemcitabine-contained comb-like copolymers poly(monomethoxyl PEG 350 methylacrylate ⿿ co - 5⿲-O-vinyladipyl- gemcitabine) (poly(mPEG 350 MA- co -VAG) and (poly(mPEG 1000 MA- co -VAG), which could self-assemble into micelles and displayed enhanced antitumor activity. The copolymers and the formed micelles were well characterized for their structure, critical aggregation concentration (CAC), morphology, cellular uptake, cell cytotoxicity, and controlled drug release. Cellular uptake and in vitro cytotoxicity assays against human lung cancerous cells (A549) demonstrated that these micelles could be effectively internalized and induced cell apoptosis. These micelles efficiently inhibited tumor growth when injected intravenously into A549 cell derived xenograft tumor bearing Balb/C nude mice using a dose of 10 mg/kg in terms of reduced tumor volume compared to free gemcitabine. In conclusion, PEGylated micelles could protect gemcitabine from rapid plasma metabolism, provided a sustained release and showed enhanced antitumor activity, thus have the potential to be used as novel anticancer drug delivery vehicle.
研究领域:
药学
·
肿瘤学
·
生物材料
✓ 已验证
DOI
高影响因子
Life-Basel
·
2026
·Vol. 16
·期 9
·1560
·
IF 3.9
Tongshan Zhu,Shumei Zhang,Mengxin Hao,Ling Wan,Fulei Nie,Guowei Zhang,Bingrui Liu,Chunyu Tian,Xinyue Wang,Haibin Liu,Yijia Li,Yuhan Feng,Di Guo,Nan Li,Yingchao Zhang,Pengcai Liu,Fan Shi,Shuoqian Ma,Rui Cao,Liangdan Sun,Xiaoming Song
Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy, and gemcitabine (GEM) resistance is a major contributor to its poor clinical outcomes, generating an urgent need for novel therapeutic strategies targeting tumor proliferation and tumor-cell-intrinsic malignant signaling. This study aimed to investigate the synergistic anti-PDAC efficacy and underlying mechanism of cepharanthine (CEP) combined with GEM. A series of in vitro and in vivo experiments were performed to evaluate the antitumor activity, synergistic effect and preliminary in vivo safety of the CEP-GEM combination. Bioinformatics analysis coupled with experimental validation was applied to dissect the underlying mechanisms. The results demonstrated that CEP produced marked synergistic effects with GEM to suppress PDAC growth both in vitro and in vivo. Mechanistic investigations revealed that CEP blocked the PI3K/AKT/mTOR pathway and reduced tumor-cell-intrinsic PD-1/PD-L1 levels, thereby facilitating tumor-cell apoptosis, restraining cell migration and invasion, and sensitizing GEM-relatively insensitive AsPC-1 cells to GEM. Under our experimental conditions, no obvious histopathological injury or prominent systemic toxicity was observed. In conclusion, this work provides preclinical evidence showing that the CEP-GEM combination exerts anti-tumor activity via dual-pathway suppression in PDAC cells, and supports further translational research for PDAC.
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DOI
高影响因子
INVESTIGATIONAL NEW DRUGS
·
2024
·
IF 3
Silli Epiphane K.,Zheng Zhenjiang,Zhou Xintao,Li Mengfei,Tang Jiali,Guo Ruizhe,Tan Chunlu,Wang Ying
Obstacles facing chemotherapeutic drugs for cancers led scientists to load Gemcitabine (GEM) into nanocarriers like liposomes, known for their nontoxicity profile and targeting capacity. The liposomal nanostructures containing GEM were coated with Fucoidan (FU) due to its anti-tumor properties by targeting cancer cells. Thus four different cationic liposomes formulations were prepared by thin-film hydration method in optimal conditions: DOTAP (formulation A); DPPC/DOTAP (4:1 molar ratio, formulation B), DPPC/DMPC/DOTAP (4:1:1 molar ratio, formulation C) and DPPC/DMPC/DOTAP/DSPE-mPEG2000 (4:1:1:0.1 molar ratio, formulation D). They were studied to identify lipid-compositions offering effective GEM-entrapment and successful coating of FU on the liposome surface. Additional qualitative characteristics, such as particle size, polydispersity index, zeta potential, stability and in vitro drug release were then evaluated. Formulation C gave the best GEM-entrapment efficiency (EE) but formed aggregates when coated with FU, giving non-homogenous large size particles then not suitable for effective delivery. It was the same situation with formulation A and B. Only the formulation D showed a good GEM-EE (> 80%) and affinity by successful coating FU from three different algae species. The PEGylated formulation D coated of FU, with regard to storage stability and drug release studies, revealed to be a promising approach on design of optimal drug delivery system.
研究领域:
药剂学
·
纳米技术
·
癌症治疗
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2014
·Vol. 4
·期 106
·61948-61959
·
IF 3.708
Manhong Tan,Jia Luo,Ying Tian
As gemcitabine and curcumin have different targets in colon cancer cells, combination of them may bring benefits. Here, curcumin and gemcitabine were formulated into a biodegradable polymer platform for combination therapy for treatment of colon cancer. In doing so, a FDA approved biodegradable polymer mPEG-PLA (methoxyl-polyethylen glycol-block-polylactide) was chosen as a drug carrier. At first, a mPEG-PLA/Gem conjugate was designed. Thereafter, simply using this drug conjugate to encapsulate curcumin, polymeric micelles loaded with both curcumin and gemcitabine were obtained. Varying the feed ratio of the two drugs, a series of micelles with different ratios of curcumin and gemcitabine could be prepared. The as-prepared dual drug loaded nanoparticles showed spherical structures with mean diameters ranging from 118 nm to 149 nm by DLS. In vitro, M(Cur/Gem) almost showed greater synergy than free combination of curcumin/gemcitabine. In vivo, better antitumor effect and lower systemic toxicity of M(Cur/Gem) were observed on a murine xenograft model. The present study provides the possibility of combining curcumin and gemcitabine in a nanoparticle formulation, and translation of this combination may bring benefits for future clinical use.
研究领域:
药剂学
·
肿瘤学
✓ 已验证
DOI
高影响因子
Cell Reports Physical Science
·
2025
·
IF 7.3
Haiyu Zhao,Wenxiao Li,Xuan Li,Zhiyu Kuang,Shengyao Xu,Zhenzhen Zhao,Jin Sun,Zhonggui He,Chunwang Fu,Yixin Sun,Bingjun Sun
Covalent albumin conjugation revolutionizes drug circulation prolongation, where binding affinity and binding sites critically govern therapeutic efficacy, but mechanisms remain unclear. Here, we report four gemcitabine (GEM) prodrugs whose pharmacodynamics and safety profiles strictly depend on the above parameters. Specifically, two prodrugs, MG and BG, employ albumin-binding modification modules derived from N-ethylmaleimide and acryloyl chloride, while others containing succinimide and propionyl chloride serve as non-albumin-binding controls. Regarding affinity, MG exhibits the highest albumin affinity, with 45-fold higher area under the curve (AUC) and 9-fold longer half-life compared to GEM, and the strongest antitumor activity. However, its reduced safety contrasts with the moderate-affinity BG, which achieves optimal efficacy-to-safety balance. Binding sites further modulate outcomes: pre-conjugation of BG to albumin remarkably increases bioavailability (23-fold higher AUC than GEM), while pre-binding of MG diminishes efficacy. These results highlight the need to optimize both binding affinity and binding sites in albumin-conjugated prodrugs.
研究领域:
药学
·
生物化学
·
肿瘤学
·
药物递送
·
药物化学
✓ 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）