JOURNAL OF CHEMICAL TECHNOLOGY AND BIOTECHNOLOGY
·
2020
·Vol. 95
·期 5
·1421-1430
·
IF 2.75
Yuanyuan Zhang,Yangjian Sun,Wenjie Ren,Qiuxiang Zhao,Kuiying Lv,Hui Tang,Xin Gao,Fengke Yang,Fanye Wang,Junhong Liu
BACKGROUND Mitomycin C (MMC) is one of the most important members of the mitomycin family that have been widely used as a strong antineoplastic antibiotic for treating various tumors. In this study, enzymatic oxidation/amination reaction of 2-methyl-1,4-hydroquinone with n -butylamine was carried out to synthesize 2-methyl-3- n -butylaminoyl-1,4-benzoquinone mitomycin analogs. RESULTS A kinetic model was developed based on an ordered sequential mechanism for this cascade reaction system catalyzed by two enzymes, which revealed that the limiting step of the system was the laccase-mediated oxidation of 2-methyl-3- n -butylaminoyl-4-hydro-1-quinone and removing the limiting step resulted in a yield increase from 88.3% to 96.7%. CONCLUSION The developed kinetic model fitted the test data very well, indicating that the reactions catalyzed by coupling of laccase with lipase might follow the ordered sequential mechanism with product inhibition. Synthesis of mitomycin analogs catalyzed by coupling of laccase with lipase has great potential for practical application. © 2020 Society of Chemical Industry
研究领域:
生物化学
·
药物化学
·
酶工程
✓ 已验证
产品关联
DOI
高影响因子
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
·
2015
·
IF 2.101
Xiu-Rong Zhang,Nian-Qiu Shi,Yang Zhao,He-Yun Zhu,Jiao Guan,Ying Jin
Mitomycin C (MTC) was incorporated to a micelle system preparing from a polymer named deoxycholic acid chitosan-grafted poly(ethylene glycol) methyl ether (mPEG-CS-DA). mPEG-CS-DA was synthesized and characterized by 1H nuclear magnetic resonance (1H-NMR) and Fourier transform infrared spectroscopy. mPEG-CS-DA formed a core-shell micellar structure with a critical micelle concentration of 6.57 µg/mL. The mPEG-CS-DA micelles were spherical with a hydrodynamic diameter of about 231 nm. After poly(ethylene glycol)ylation of deoxycholic acid chitosan (CS-DA), the encapsulation efficiency and drug loading efficiency increased from 50.62% to 56.42% and from 20.51% to 24.13%, respectively. The mPEG-CS-DA micelles possessed a higher drug release rate than the CS-DA micelles. For pharmacokinetics, the area under the curve (AUC) of the mPEG-CS-DA micelles was 1.5 times higher than that of MTC injection, and these micelles can enhance the bioavailability of MTC. mPEG-CS-DA micelles reduced the distribution of MTC in almost all normal tissues and had the potential to improve the kidney toxicity caused by MTC injection.
研究领域:
药剂学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Omega
·
2026
·
IF 5.2
Huanhuan Xu,Liang Lu,Xueying Kong,Rui Wu,Hu Meng,Dekui Ren,Jun Gu,Yong Wu,Yirui Ge
Canalicular lacerations represent a common ocular emergency that can lead to significant complications if not managed promptly and effectively. Silicone stents are the most commonly chosen option due to their favorable characteristics. However, postoperative complications, such as canalicular stenosis, remain prevalent, necessitating the exploration of additional therapeutic strategies. Mitomycin C (MMC) is an effective agent for preventing excessive fibrosis in various ophthalmic surgeries; however, its topical application faces challenges due to rapid clearance and potential side effects. Currently, we have established a dual-layer drug delivery system for MMC, wherein lacrimal drainage catheters (LDC) were coated with agarose loaded with MMC (MA-1, MA-2, and MA-3) and subsequently encapsulated in a layer of poly(lactic-co-glycolic acid) (PLGA). The LDC@MA-1@PLGA, LDC@MA-2@PLGA, and LDC@MA-3@PLGA released final amounts of MMC of 1.72 ± 0.21 μg, 5.32 ± 0.56 μg, and 9.32 ± 0.16 μg during the first 8 days, with corresponding final release rates of 57.43 ± 7.78%, 85.36 ± 10.49%, and 79.06 ± 2.56%, respectively. In vitro assays demonstrated that MMC not only inhibits fibroblast proliferation but also enhances apoptosis, particularly in the fibrotic context induced by TGF-β1. Additionally, in vivo experiments demonstrated that LDC@MA@PLGA effectively reduced the expression levels of α-SMA and collagen deposition. Overall, the findings from our study elucidate the potential of LDC@MA@PLGA as an effective therapeutic strategy in preventing postsurgical fibrosis following canalicular laceration repairs.
✓ 已验证
DOI
PubMed
高影响因子
Biomaterials Advances
·
2025
·
IF 6
Jingyi Ma,Lu Wang,Aimeng Dong,Shiqi Zhang,Tao Guo,Yiling Han,Menglu Jiang,Pan Fan,Wulian Song,Fenghua Zhang,Jinsong Leng,Huiping Yuan
Bleb fibrosis remains the most common reason for glaucoma surgery failure. Although mitomycin C (MMC) is often used to inhibit fibrosis during glaucoma drainage device (GDD) implantation, the effective reaction time of anti-fibrosis could not cover the dynamic process of wound healing. To enable noninvasive dynamic ocular drug release, we fabricated MMC-loaded thermos-responsive fiber membranes using polylactic acid (PLA) and tributyl citrate as a plasticizer. The fibers exhibited a transition temperature of 41.5 °C. To regulate drug delivery, the fiber was first stretched, coated on the GDD surface, and then implanted in rabbit eyes. The thermal-responsive fiber recovered to its original morphology upon exposure to a 43 °C stimulus in filtering bleb area one week postoperatively. The release profiles in vitro were described best by the first-order kinetics. The release rate constants were k origin = 0.11 ± 0.01 day −1 and k stretched = 0.09 ± 0.02 day −1 , respectively. The controlled release system effectively reduced the bleb fibrosis in rabbit conjunctiva. This MMC-controlled delivery system successfully inhibited scarring after GDD implantation surgery.
研究领域:
眼科
·
生物材料学
·
药剂学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Omega
·
2020
·
IF 2.87
Yan Xu,Xiangmei Jin,Jun Zhang,Kun Wang,Xiaoyan Jin,Dongyuan Xu,Xizhe Tian,Lan Liu
In this study, we designed, formulated, and investigated the potential antitumor activity of a folate receptor (FR)-mediated double-targeted drug delivery system. The system comprised of the FR ligand folic acid (FA), glycine-phenylalanine-leucine-glycine (Gly-Phe-Leu-Gly, GFLG), which can be specifically cleaved by cathepsin B, and the anticancer drug mitomycin C (MMC). The antitumor effect of FA-GFLG-MMC was compared to that of MMC. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay revealed that FA-GFLG-MMC has a significantly higher inhibitory effect on HeLa, SiHa, and PC9 cells (high FR expression) than that on 16HBE and A549 cells (low FR expression). Furthermore, FA-GFLG-MMC inhibited cancer cell proliferation in a dose-dependent manner. Free MMC was toxic to both cancer and normal cells. Apoptosis of the HeLa, SiHa, and PC9 cells was higher than that of the A549 cells; however, the apoptotic effect on 16HBE cells was minimal. Proapoptotic protein bcl-2-associated X-protein (BAX) and antiapoptotic protein BCL-2 play critical roles in cellular defense and apoptotic signal transduction. BAX/BCL-2 ratio is used to determine the intensity of an apoptotic signal and assess whether a cell will survive or undergo apoptosis. BAX and BCL-2 expression in cells treated with 5 μM FA-GFLG-MMC was studied by Western blotting. FA-GFLG-MMC increased the BAX/BCL-2 ratio in HeLa, SiHa, and PC9 cells. The results show that FA-GFLG-MMC can effectively inhibit tumor cell proliferation by inducing apoptosis. Therefore, the system developed can enhance the delivery of anticancer drugs to cancer cells and thereby reduce their toxic effects on normal cells.
研究领域:
药理学
·
肿瘤学
·
药物递送系统
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2023
·
IF 4.9
Rui Chang,Rongrong Fu,Yujiao Huang,Jibing Zhang,Changshun Feng,Rui Wang,Hui Yan,Guangyong Li,Xiaohong Chu,Fengjiao Yuan,Dianlong Jia,Jun Li
Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) constitutes a promising antitumor drug, tumor resistance to TRAIL has become a major obstacle in its clinical application. Mitomycin C (MMC) is an effective TRAIL-resistant tumor sensitizer, which indicates a potential utility of combination therapy. However, the efficacy of this combination therapy is limited owing to its short half-life and the cumulative toxicity of MMC. To address these issues, we successfully developed a multifunctional liposome (MTLPs) with human TRAIL protein on the surface and MMC encapsulated in the internal aqueous phase to codeliver TRAIL and MMC. MTLPs are uniform spherical particles that exhibit efficient cellular uptake by HT-29 TRAIL-resistant tumor cells, thereby inducing a stronger killing effect compared with control groups. In vivo assays revealed that MTLPs efficiently accumulated in tumors and safely achieved 97.8% tumor suppression via the synergistic effect of TRAIL and MMC in an HT-29 tumor xenograft model while ensuring biosafety. These results suggest that the liposomal codelivery of TRAIL and MMC provides a novel approach to overcome TRAIL-resistant tumors.
研究领域:
药理学
·
肿瘤学
·
药物递送系统
·
生物技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Molecular Biosciences
·
2021
·
IF 5.246
Zhang Yin,Wang Qinge,Xu Yuping,Sun Jing,Ding Yanbo,Wang Li,Chen Bingfang,Sun Kewen,Chen Jianping
Benign esophageal strictures (BESs) frequently results from esophageal fibrosis. The transformation of fibroblasts into fibrocyte is an important cause of fibrosis. The treatment of fibrosis is challenging. Some previous studies have indicated the antifibrotic effect of mitomycin C (MMC). However, the mechanism of action of MMC and its optimal dose for treatment remains unclear. In the present study, the role of MMC in fighting fibrosis and its mechanism was investigated. Human esophageal fibroblast cells (HEFs)were treated without or with MMC, at 2, 5, 10 μg/ml, combining with mimic lncRNA-ATB, miR-200b inhibitor, rapamycin (RAPA), and 3-Methyladenine (3-MA). The cell viability, and cell apoptosis were evaluated. In addition, expression of apoptosis related proteins (caspase8 and caspase3), autophagy related proteins (LC3II and ATG5) and fibrosis related proteins (α-SMA collagen-1 and TGF-β) were also evaluated. Furthermore, autophagosome was observed by transmission electron microscope. Results showed that the expression of lncRNA-ATB was down-regulated and miR-200b was up-regulated after treated with MMC. And MMC induced cell apoptosis and inhibited cell autophagy. On the other hand, RAPA, mimic lncRNA-ATB and miR-200b inhibitor reduced fibrogenic effect of MMC on HEFs. Collectively, this study suggests that MMC inhibited esophageal fibrosis by regulating cell apoptosis and autophagy via downregulating lncRNA-ATB and upregulating miR-200b.
研究领域:
药理学
·
分子生物学
·
细胞生物学
·
病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2015
·
IF 4.152
Jixiang Zhu,Fanwen Yang,Fupo He,Xiumei Tian,Shuo Tang,Xiaoming Chen
A tubular gelatin scaffold for the time-dependent controlled release of epidermal growth factor (EGF) and mitomycin C (MMC) was fabricated. EGF was incorporated using silk fibroin carriers, and MMC was planted using polylactide (PLA) microspheres. The relationship between scaffold properties and crosslinking degrees was evaluated. As the crosslinking degree was increased from 23.7% to 65.3%, the mechanical properties of the scaffold obviously improved, and the compressive modulus increased to approximately 65 kPa. The mass degradation of the scaffold was also controlled from 9 days to approximately 1 month. In vitro release tests indicated that the scaffold mainly released EGF in the early period and MMC in the later period. Urethral epithelial cells (UECs) and urethral scar derived fibroblast cells (UFCs) were coseeded in the scaffold at a ratio of 1:1. After 9 days of coculture, immunostaining results displayed that the proportion of UECs continuously increased to approximately 71%. These changes in cell proportion were confirmed by the results of Western blot analysis. Therefore, the scaffold promoted the growth but inhibited the regeneration of UFCs. This scaffold for time-dependent controlled release of multiple biofactors may be potentially useful in urethral reconstruction and other tissue engineering studies.
研究领域:
生物医学工程
·
组织工程
·
药理学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF POROUS MATERIALS
·
2022
·Vol. 29
·期 5
·1489-1505
·
IF 2.523
Chang Ziling,Li Huafei,Yang Yuxiang,Yuan Hongming,Huang Yan,Yao Pingping,Ni Chaoying
Herein, we developed the dual-function template method to fabricate hollow magnetic nano-spheres (denoted as HMFe–Si–C n , n = 16, 18) with a mesoporous shell and hollow interior structure using alkyl chain trimethoxysilane templating. The shorter chain template directed formation of HMFe–Si–C 16 with size of 119 nm, having disordered inkbottle type mesopores and saturation magnetization of 50.01 emu/g higher than that of HMFe–Si–C 18 with cylindrical type mesopores. In addition, the HMFe–C n loaded with MMC diaplays a pH and magnetic dual responsive drug release behavior. By contrast, Mitomycin C (MMC) loading efficiency of HMFe–Si–C 16 was higher owing to the fact that the pore size, surface area, and pore volume of HMFe–Si–C 16 were larger than those of HMFe–Si–C 18 . Besides, MMC loaded HMFe–Si–C n hollow spheres showed a clear pH-dependent drug release behavior, having a higher release rate in acidic environments of pH 5.7. For the pH 5.7 and 7.4 release, the release kinetic for HMFe–Si–C 16 –MMC composites follows pseudo-first-order attributable to its special pore structure. With Fe(0) as a core, HMFe–Si–C n is distinguished for higher magnetic properties, and it is more conducive to magnetic targeted treatment of cancer cells and can release drugs through external magnetic field. In addition, HMFe–Si–C n has lower cytotoxicity and better biocompatibility. For this reason the inner cavity of HMFe–Si–C 16 could be labeled with radioisotope 99 Tc m to study the magnetic targeting distribution of HMFe–Si–C 16 in vivo, and its cytotoxicity against in vitro HeLa cells was also studied. These results indicate the potential of HMFe–Si–C 16 in the magnetic targeted drug delivery system.
研究领域:
纳米材料
·
药物递送系统
·
肿瘤治疗
✓ 已验证
产品关联
DOI
高影响因子
EXPERIMENTAL EYE RESEARCH
·
2020
·
IF 3.011
Mengliang Wu,Shangfeng Wang,Yan Wang,Fan Zhang,Tingting Shao
Pterygium is a degenerative disease that characterized by excessive fibrovascular proliferation. To reduce the recurrence rate, surgery is the main strategy, in combination with adjacent procedures or adjunctive therapy. One of the most common adjunctive agents, mitomycin C (MMC), is known as an alkylating agent that inhibits fibroblast proliferation but is limitedly applied in pterygium due to various complications. A previous study demonstrated that activated pterygium subconjunctival fibroblasts overexpressed low-density lipoprotein (LDL) receptors. In this study, we designed and synthesized MMC-loaded mesoporous silica nanoparticles conjugated with LDL (MMC@MSNs-LDL) to deliver MMC into activated pterygium fibroblasts in a targeted manner. The MMC loading efficiency was approximately 6%. The cell viability test (CCK-8 assay) revealed no cytotoxicity for the empty carrier MSNs at a concentration of ≤1 mg/ml after administration for 48 h in subconjunctival fibroblasts. Primary pterygium and normal human subconjunctival fibroblasts with or without stimulation by vascular endothelial growth factor (VEGF) were treated as follows: 1) 10 μg/ml MMC@MSNs-LDL for 24 h (MMC concentration: 0.6 μg/ml); 2) 0.2 mg/ml MMC for 5 min then cultured for 24 h after MMC removal; and 3) normal culture without any drug treatment. At 24 h, the anti-proliferative effect of MMC@MSNs-LDL in activated pterygium fibroblasts was similar to that of MMC (cell viability: 46.2 ± 5.5% vs 40.5 ± 1.1%, respectively, P = 0.349). Furthermore, the cytotoxicity of MMC@MSNs-LDL to normal fibroblasts with or without VEGF stimulation was significantly lower than that of traditional MMC (cell viability: 75.6 ± 4.4% vs 36.0 ± 1.5%, respectively, P < 0.001; 84.7 ± 5.5% vs 35.7 ± 1.3%, P < 0.001). The binding of fluorescently labeled MMC@MSNs-LDL in fibroblasts was assessed using confocal fluorescence microscopy . The uptake of targeted nanoparticles in fibroblasts was time dependent and saturated at 6 h. VEGF-activated pterygium fibroblasts showed more uptake of MMC@MSNs-LDL than normal fibroblasts with or without VEGF activation (both P < 0.001). Our data strongly suggest that MMC@MSNs-LDL had an effective antiproliferative role in activated pterygium fibroblasts, with reduced toxicity to normal fibroblasts compared to traditional application of MMC. LDL-mediated drug delivery might have great potential in the management of pterygium recurrence.
研究领域:
眼科
·
药剂学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2014
·Vol. 8
·期 3
·935-942
·
IF 0.941
Wei Zhang,Jiabo Hu,Quanhui Ma,Sanqiang Hu,Yanyan Wang,Xiangmei Wen,Yongbin Ma,Hong Xu,Hui Qian,Wenrong Xu
An immortalized mouse fetal liver stromal cell line, named KM3, has demonstrated the potential to support the growth and maintenance of human embryonic stem cells (hESCs). In this study, the characteristics of KM3 cells were examined following cryopreservation at -70˚C and in liquid nitrogen for 15, 30 and 60 days following treatment with 10 µg/ml mitomycin C. In addition, whether the KM3 cells were suitable for use as feeder cells to support the growth of hESCs was evaluated. The inhibition of mitosis without cell death was observed when the KM3 cells were treated with 10 µg/ml mitomycin C for 2 h. The morphology of the KM3 cells cryopreserved in liquid nitrogen for 60 days was not markedly changed, and the cell survival rate was 84.60±1.14%. By contrast, the survival rate of the KM3 cells was 66.40±2.88% following cryopreservation at -70˚C for 60 days; the cells readily detached, were maintained for a shorter time, and had a reduced expression level of basic fibroblast growth factor. hESCs cultured on KM3 cells cryopreserved in liquid nitrogen for 60 days showed the typical bird's nest structure, with clear boundaries and a differentiation rate of 16.33±2.08%. The differentiation rate of hESCs cultured on KM3 cells cryopreserved at -70˚C for 60 days was 37.67±3.51%. These results indicate that the cryopreserved KM3 cells treated with mitomycin C may be directly used in the subculture of hESCs, and the effect is relatively good with -70˚C short-term or liquid nitrogen cryopreservation.
研究领域:
干细胞生物学
·
细胞培养
·
低温生物学
✓ 已验证
DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2026
·
IF 5.2
Haiyan Wu,Jianlei Wu,Nian Huang,Jean-François Masson,Haifeng Zhou,Wenjuan Zhou,Wei Lin,Guobin Liang
A sensitive ratiometric electrochemical strategy for MMC detection is developed. • Polythionine serves as an internal reference for improved response stability. • Ce-Ni-MOF/MWCNTs enhance interfacial electron transfer. • Molecular imprinting enables selective MMC recognition. • MMC detection is validated by UPLC-QTOF-MS in water samples. Mitomycin C (MMC) is a widely used antitumor antibiotic, and its rapid and selective detection is crucial for monitoring its occurrence in environmental water samples. In this work, a ratiometric electrochemical sensor was constructed by sequential modification of a bimetallic Ce-Ni-metal-organic framework (Ce-Ni-MOF)/multi-walled carbon nanotube (MWCNTs) composite, polythionine (pThi) and a molecularly imprinted polymer (MIP) on a glassy carbon electrode. The Ce-Ni-MOF/MWCNTs composite facilitated electron transfer, contributing to the enhanced sensitivity of the sensing platform. The pThi was electropolymerized onto the modified electrode surface to provide an internal reference signal, while the ratiometric response was achieved through two electrochemical channels, with the [Fe(CN)₆] 3−/4 − redox probe serving as the response signal and the pThi signal as the reference, enabling effective correction of measurement variations. Under optimized conditions, the sensor exhibited a linear response to MMC over the concentration range of 0.1–100 nM, with a low detection limit of 0.046 nM and a limit of quantification of 0.075 nM. Owing to the specific molecular recognition of the MIP layer and the internal reference function of pThi, the proposed sensor demonstrated satisfactory selectivity, repeatability, reproducibility and stability. Furthermore, the sensor was successfully applied to the determination of MMC in water samples, achieving recoveries of 87–112%. The analytical performance of the proposed sensor was further validated by comparison with the results obtained using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). This work presents a reliable and sensitive ratiometric electrochemical sensing strategy and demonstrates its feasibility through a proof-of-concept study for MMC detection in environmental water samples. Download: Download high-res image (304KB) Download: Download full-size image
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）