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
Materials Express
·
2023
·Vol. 13
·期 2
·312-315
·
IF 0.7
Pan Jie,Cui Liang,Liu Si-Han
Lung cancer is currently the most common malignant tumor and most lethal cancer worldwide, posing a serious threat to human life and health. Mitomycin has been widely used in the clinical treatment of malignant tumors owing to its strong antitumor effects. In this study, hyaluronic
acid/carboxymethyl chitosan hydrogels loaded with mitomycin were prepared by chemical synthesis. The SEM results showed that the hydrogels had a 3D interoperable porous structure, which facilitates drug loading. Biological experiments showed that the mitomycin-loaded hydrogels remarkably reduced
the viability of cancer cells and inhibited the activation of the VEGF signaling pathway in cancer cells in a dose-dependent manner. Thus, the hydrogels are expected to be used as a drug carrier material for lung cancer treatment.
研究领域:
肿瘤学
·
药剂学
·
生物材料学
✓ 已验证
产品关联
DOI
高影响因子
ENGINEERING IN LIFE SCIENCES
·
2019
·Vol. 19
·期 11
·805-814
·
IF 1.936
Yuanyuan Zhang,Quancai Yao,Zewen Li,Fengke Yang,Fanye Wang,Junhong Liu
To reach the excellent yield as well as environmental friendliness, an efficient one-pot process for the synthesis of 2-methyl-3- n- butylaminoyl-1,4-benzoquinone, a mitomycin-like compound by the domino reaction of 2-methyl-1,4-hydroquinone and butylamine using laccase/lipase as co-catalysts, has been developed. In this present study, the process proposed here was further improved by optimizing the relevant factors using the response surface methodology based on Box–Benkhen Design. The optimum condition that afforded the highest yield (98%) of 2-methyl-3- n- butylaminoyl-1,4-benzoquinone was obtained as follows: molar ratio of amines to hydroquinones 1.16:1, activity ratio of laccase to lipase 1.14:2, and reaction temperature 38.9°C. The results obtained indicate that this process may be useful as a green alternative method for higher yield production of mitomycin analogs.
研究领域:
生物化学
·
药物合成
·
环境科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2025
·
IF 5.6
Xionghua Sun,Xuelei Wan,Li Chen,Yadong Cui,Xihua Chen,Jian Zhang,Xiaogang Jiang
The senescence of alveolar epithelial cells is one of the characteristics of mitomycin pulmonary toxicity, but the direct target of mitomycin-induced alveolar epithelial cell senescence remains unclear. In this study, a method of small-molecule ligand–protein interaction by pulldown/mass spectrometry identified peroxiredoxin I (Prdx I) as the target of mitomycin-induced alveolar epithelial cell senescence, and mitomycin was shown to significantly inhibit the peroxidase activity of Prdx I. Consequently, the levels of cellular reactive oxygen species (ROS) increased, leading to the activation of mitogen-activated protein kinase kinase 1/2 (MEK1/2)-extracellular signal-regulated protein kinases 1/2 (ERK 1/2) and, accordingly, to the increased expression of p53. Both a Prdx I activator and Prdx I overexpression alleviated mitomycin-induced alveolar cell senescence. A ROS scavenger inhibited MEK1/2-ERK1/2-p53 activation and then attenuated the senescence of alveolar epithelial cells triggered by mitomycin. Thus, Prdx I can serve as the first target of mitomycin-induced alveolar epithelial cell senescence, which might represent a promising approach to reduce mitomycin-induced lung toxicity.
研究领域:
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
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
RSC Advances
·
2019
·Vol. 9
·期 26
·14708-14717
·
IF 3.049
Hongmei Yang,Miao Wang,Yihe Huang,Qiaoyu Qiao,Chunjie Zhao,Min Zhao
Mitomycin C (MMC), naturally synthesized by Streptomyces caespitosus, is a potent antineoplastic antibiotic for the treatment of various solid tumors. However, the defects of conventional MMC injections have greatly limited its clinical application due to its toxic side effects and non-specific interactions. To solve this problem, the PEG2k-Fmoc-Ibuprofen (PEG-FIbu) micellar nanocarrier was synthesized and the MMC-loaded micelles (PEG-FIbu/MMC) were prepared by thin film hydration method and characterized. Ibuprofen was used as a hydrophobic domain of PEG-FIbu nanocarrier, and we expect it to synergize with codelivered MMC in the overall antitumor activity. The in vitro release of PEG-FIbu/MMC was examined by dialysis method using MMC injection as a control. Our data suggested that PEG-FIbu/MMC micelles presented appropriate particle size, low CMC value, good stability, high drug loading efficiency and sustained release properties. In vitro cytotoxicity studies with several tumor cell lines showed that the carrier was effective in mediating intracellular delivery of MMC to tumor cells. In vivo pharmacokinetics, tissue distribution and therapeutic study proved that PEG-FIbu/MMC micelles prolonged blood circulation, significantly improved the tumor accumulation and therapeutic efficacy, and reduced undesirable side effect on normal tissues compared to MMC injection. In general, PEG-FIbu/MMC micelles represented an effective strategy to improve the performance for the delivery of MMC and safety of medication.
研究领域:
药学
·
肿瘤学
·
纳米技术
·
药物递送系统
✓ 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
International Journal of Nanomedicine
·
2026
·
IF 8.7
Congcong Yang,Jianyou Xia,Lunjie Zhao,Jianping Tao,Dan Li,Renxi Zhu,Qiang Wang,Haichen Shen,Baochao Zhang,Yujie Xu
Background In recent years, bladder defect repair has emerged as a critical issue in urological tissue engineering. Traditional treatment methods, such as autologous tissue transplantation and synthetic material repair, are limited by factors such as scarce donor sources, immune rejection, and postoperative fibrosis. Consequently, the development of nanofiber materials with bionic structures, biocompatibility, and anti-fibrotic capabilities has become a research hotspot. This research addressed the clinical needs associated with tuberculous bladder contracture, chronic cystitis, traumatic bladder rupture, and malignant tumors requiring partial cystectomy (such as localized non-muscle-invasive bladder cancer and urachal cancer), among other conditions. Excessive fibrotic scar formation following bladder surgery or injury is a primary contributor to reduced bladder compliance, diminished capacity, and impaired contractile function.Methods Using electrospinning technology, we designed and prepared composite nanofibers with varying proportions (9:1, 7:3, 5:5) of polycaprolactone (PCL) and gelatin (GEL). By conducting various experiments such as scanning electron microscopy (SEM), water contact angle (WCA) analysis, mechanical performance evaluation, and Fourier transform infrared spectroscopy (FTIR), the PCL/GEL (7:3) composite material was ultimately selected as the one with the best overall performance.Results Its fiber diameter was 612.14 ± 105.46 nm, water contact angle was 107.23°, and mechanical properties (tensile strength: 3.84 ± 0.5 MPa, elongation at break: 118.42 ± 4%, Young’s modulus: 19.50 ± 4.6 MPa). To enhance its anti-fibrotic properties, we incorporated mitomycin C (MMC) into the nanofiber matrix and prepared PCL/GEL/MMC nanofiber materials through blending and spinning. We then established a partial cystectomy model in rats, implanted the PCL/GEL/MMC nanofiber materials, and performed bladder imaging four weeks post-surgery to assess bladder capacity and morphological recovery. The CCK-8 assay was performed on days 1, 3, and 7, demonstrating that smooth muscle cells (SMCs) and endothelial cells (ECs) can effectively adhere, survive, and proliferate on these fibrous membranes, thereby confirming their biocompatibility. The anti-fibrotic properties of the materials were evaluated using immunofluorescence staining (IF)and immunohistochemical analysis (IHC).Conclusion The experimental results demonstrated that PCL/GEL nanofiber materials loaded with 0.02% MMC exhibited excellent biocompatibility and anti-fibrotic effects in bladder defect repair, providing a theoretical basis for their potential clinical application.
✓ 已验证
产品关联
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
危险品化学品经营许可证（带存储）