ChemistrySelect
·
2023
·Vol. 8
·期 43
·e202300464
·
IF 2.1
Xiangdong He,Mengke Xu,Xicheng Liu,Yihong Wang
Graphical Two organo-bimetallic complexes of ferrocene and organotin were synthesized and their chemical purity was verified. The results of cytotoxicity test confirmed that the complex had good antitumor activity against various tumor cell lines. The ability of the complex to induce immunogenic cell death was confirmed by a series of cellular mechanism experiments. The synthesis of this drug provides hope for solving the resistance of the clinical drug cisplatin. Two organo-bimetallic complexes of ferrocene and organotin were synthesized and evaluated as potential anticancer drugs. MTT results indicated that the two complexes showed excellent antitumor activity against a variety of cancer cell lines compared with cisplatin and ferrocene alone. Different from the previous similar metal drugs available, the complexes synthesized in this work have a concentration-dependent effect on immunogenic cell death (ICD) related proteins and the level of adenosine triphosphate(ATP) intracellular. The up-regulation of related proteins leads to the imbalance of mitochondrial homeostasis, and the destruction of the electron transport chain which causes the accumulation of reactive oxygen species(ROS)in the mitochondria and induces cell death. In the wound healing assay, the complex can effectively inhibit the growth and reproduction of cells. The promising results displayed by the organo-bimetallic complexes open avenues for new anticancer drugs.
研究领域:
化学
·
药理学
·
肿瘤学
·
免疫学
✓ 已验证
DOI
高影响因子
CURRENT MEDICINAL CHEMISTRY
·
2024
·
IF 3.5
Gan Xin,Xie Jingwen,Dong Zhaojun,Wu Yuna,Zeng Xiaoqing,Yang Zhenzhen,Liu Bo,Zhu Min,Wang Bozhen,Li Wulan,Wang Ledan,Zhang Huajie,Wu Jianzhang,Hu Yue
Background: Pyroptosis, a cell death process triggered by chemotherapy drugs, has
emerged as a highly promising mechanism for combating tumors in recent years. As the lead of
new drugs, natural products play an important role in the discovery of anticancer drugs. Compared
to other natural products, the medicine food homologous natural products (MFHNP) exhibit a superior
safety profile. Among a series of MFHNP molecular skeletons, this study found that only
benzylideneacetophenone (1) could induce cancer cell pyroptosis. However, the anti-cancer activity
of 1 remains to be improved.
Aims: This study aimed to find a pyroptosis inducer with highly effective antitumor activity by
modifying the chalcone structure.
Methods: To examine the effect of the Michael receptor in compound 1 on the induction of pyroptosis,
several analogs were synthesized by modifying the Michael acceptor. Subsequently, the anticancer
activity was tested by MTT assay, and morphological indications of pyroptosis were observed
in human lung carcinoma NCI-H460 and human ovarian cancer CP-70 cell lines. Furthermore,
to improve the activity of the chalcone skeleton, the anticancer group 3,4,5-
trimethoxyphenyl was incorporated into the phenyl ring. Subsequently, compounds 2-22 were designed,
synthesized, and screened in human lung cancer cells (NCI-H460, H1975, and A549). Additionally,
a quantitative structure-activity relationship (QSAR) model was established using the
eXtreme Gradient Boosting (XGBoost) machine learning library to identify the pharmacophore.
Furthermore, both in vitro and in vivo experiments were conducted to investigate the molecular
mechanisms of pyroptosis induced by the active compound.
Results: α, β-unsaturated ketone was the functional group of the chalcone skeleton and played a
pivotal role in inducing cancer cell pyroptosis. QSAR models showed that the regression coefficients
(R2) were 0.992 (A549 cells), 0.990 (NCI-H460 cells), and 0.998 (H1975 cells). Among these
compounds, compound 7 was selected to be the active compound. Moreover, compound 7 was
found to induce pyroptosis in lung cancer cells by upregulating the expression of CHOP by increasing
the ROS level. Furthermore, it effectively suppressed the growth of lung cancer xenograft
tumors.
Conclusion: Compound 7 exhibits antineoplastic activity by regulating the ROS/ER stress/pyroptosis
axis and is a kind of promising pyroptosis inducer.
研究领域:
肿瘤学
·
药理学
·
药物化学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
RSC Advances
·
2020
·Vol. 10
·期 60
·36862-36872
·
IF 3.119
Mengru Cai,Liuying Qin,Longtai You,Yu Yao,Huimin Wu,Zhiqin Zhang,Lu Zhang,Xingbin Yin,Jian Ni
Metal organic frameworks (MOFs) are widely used in drug carrier research due to their tunability. The properties of MOFs can be adjusted through incorporation of mono-substituents to obtain pharmaceutical carriers with excellent properties. In this study, different functional groups of –NH2, –CH3, –Br, –OH and –CH2CH are connected to MOF-5 to analyse the effect of mono-substituent incorporation on drug delivery properties. The resulting MOFs have similar structures, except for Br–MOF. The pore size of this series of MOFs ranges from 1.04 nm to 1.10 nm. Using oridonin (ORI) as a model drug, introduction of the functional groups appears to have a significant effect on the drug delivery performance of the MOFs. The IRMOFs can be ranked according to drug-loading capacity: MOF-5 > HO–MOF-5 > H3C–MOF-5 = Br–MOF-5 > H2N–MOF-5 > CH2CH–MOF-5. The ORI release from ORI @IRMOFs is explored at two different pH values: 7.4 and 5.5, and the ORI@IRMOFs are ranked according to the cumulative release percentage of ORI: ORI@MOF-5 > ORI@Br–MOF-5 > ORI@H3C–MOF-5 > ORI@H2N–MOF-5 > CH2CH–MOF-5 > ORI@ HO–MOF-5. In particular, the release behaviour of ORI@MOFs is described through a new model. The different drug delivery performance of MOFs may be due to the complex interactions between MOFs and ORI. In addition, the introduction of single substituents does not change the biocompatibility of MOFs. MTT in vitro experiments prove that this series of MOFs has low cytotoxicity. This study shows that the incorporation of single substituents can effectively adjust the drug delivery behaviour of MOFs, which is conducive to realization of personalized drug delivery modes. The introduction of active groups can also facilitate post-synthesis modification to achieve coupling of targeting groups. MOFs incorporated with single substituents perform favorably in terms of use as biomedical drug delivery alternative carriers in effective drug payload and flexible drug release.
研究领域:
材料科学
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INORGANICA CHIMICA ACTA
·
2018
·
IF 2.264
Yang Zhang,Jian Wang
A water-stable 2D Zn-based MOF with chemical formulae [(Me 2 NH 2 ) 4 Zn 2 (FDC) 4 ] n ( 1 ) (FDC = 2,5-furandicarboxylate) was synthesized and structurally characterized. TGA and PXRD results show high thermal and water stability for 1 . 1 exhibits a 2D (4,4) net with 1D channel of 7.2 × 7.2 Å 2 along the c axis. Desolvated 1 adsorbs around 11.4 wt% 5-Fluorouracil and the cumulative release value of 5-Fluorouracil at 48 h was about 96.5% and 99% in PBS (pH = 7.4 and pH = 6.0) at 37 °C, respectively. The in vivo Zebrafish toxicity tests and in vitro MTT assays of 1 at different concentrations results reveal that 1 is nontoxic.
研究领域:
材料科学
·
药学
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
·
2022
·
IF 5.518
Zhengwei Xu,Xiaohong Jiang
The purpose of the nano-porous TiO 2 modification on TC26 (Ti-13 Nb-13Zr) alloy is to settle the issue that the surface inertness of titanium alloys restricts bioactivity and osseointegration of artificial implants . Secondary constant current anodization was conducted to realize the efficient fabrication of the TiO 2 composite nano-porous arrays containing the terminal small-diameter nanopores and the upper large-diameter nanotubes . The oxygen bubble mould theory has revealed the anodization mechanism of the TiO 2 nano-porous arrays. The anodization parameters and heat treatment conditions are both able to elicit influence on morphology, chemical composition , surface properties and biocompatibility of the as-fabricated samples. The interaction of MC3TC-E1 mouse pre-osteoblasts with a series of TiO 2 nano-porous arrays fabricated by primary anodization (PA) and secondary anodization (SA) was investigated by the MTT assay and alkaline phosphatase (ALP) activity assay. The response of the seeded MC3TC-E1 pre-osteoblasts to the as-fabricated samples with various nano-scale dimensions has indicated that appropriate nano-porous morphologies and heat treatment conditions have the capacity to augment cell adhesion, growth, differentiation and functionality. Such fabrication route in this research has provided a promising prospect for development of artificial implants.
研究领域:
材料科学
·
生物材料
·
生物医学工程
·
细胞生物学
✓ 已验证
DOI
高影响因子
JOURNAL OF CLUSTER SCIENCE
·
2024
·
IF 2.7
Luo Honghuan,Chen Menglan,Song Fangxiang,Cai Xiaoqin,Yan Yibing,Li Tingxian,Songye Li,Li Yan
Zeolitic imidazolate framework-8 (ZIF-8) is a promising material for drug delivery, but its poor stability limits its wide application. In this work, homogeneous dodecahedral ZIF-8 was prepared by the room-temperature solution stirring method, and to improve the stability of ZIF-8, ZIF-8@mSiO 2 and DZIF-8 (ZIF-8 after calcination) @PMO composites with the core-shell structure were obtained using mesoporous silica (mSiO 2 ) and periodic mesoporous organic silica (PMO) coatings. Folic acid-coupled chitosan (CS-FA) was modified on nanoparticles, and curcumin (CUR) was used as a model anti-tumor drug to obtain the drug delivery systems with targeting and pH stimulation response: ZIF-8@mSiO 2 @CUR@CS-FA and DZIF-8@PMO@CUR@CS-FA, which exhibited good dispersion and high drug loading capability. In addition, we used the MTT assay to assess the cytotoxicity of the drug-carrying systems and selected human cervical cancer cells (Hela) as model cells. The results of the in vitro experiments suggested that the final CUR-loaded drug delivery systems had significantly increased anticancer efficiency compared with the free drug CUR, which improved the therapeutic effect of the hydrophobic CUR on tumors. In conclusion, the pH-responsive nanocarriers provided potential for the targeted delivery of anticancer medication, resulting in a platform for drug-controlled release and cancer therapy.
研究领域:
纳米技术
·
药物递送系统
·
癌症研究
·
材料科学
·
药学
✓ 已验证
DOI
高影响因子
BIOMACROMOLECULES
·
2024
·
IF 5.5
Xiaoya Li,Qian Zhang,Weidong Wu,Jinxin Lin,Yingchun Liu,Liheng Chen,Xueqing Qiu
Nitric oxide (NO) has received growing attention as an effective antibacterial agent with broad-spectrum activity and a low risk of resistance. However, it remains challenging to develop effective, controllable, and biocompatible NO-releasing materials. Here, we report a novel NO nanogenerator (AL-BNN6-PEG) self-assembled by lignin, a UV-absorbing and hydrophobic NO donor (N,N′-disec-butyl-N,N′-dinitroso-1,4-phenylenediamine, BNN6), and PEG-DSPE2000. It was discovered that upon visible light irradiation (450–460 nm), BNN6 can be decomposed by lignin within micellar nanoparticles via a photoinduced electron transfer mechanism in the aqueous medium. Lignin not only served as a sustainable carrier, enhancing the water dispersity of BNN6, but also acted as a biocompatible photosensitizer, triggering BNN6 decomposition with the concomitant release of NO. As a result, the micellar nanoparticles displayed superior antibacterial effects against Gram-negative and Gram-positive bacteria upon visible light illumination. Moreover, MTT assay revealed the negligible cytotoxic effect of the micellar nanoparticles to the mouse fibroblast cells (L929). This research provides more insight into the BNN6 decomposition mechanism and demonstrates a straightforward, effective, and biocompatible strategy for controlled NO-mediated antibacterial applications.
研究领域:
材料科学
·
生物医学工程
·
药学
·
微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
·
2013
·
IF 7.604
Feifei Yang,Wei Huang,Yunfei Li,Shan Liu,Mingji Jin,Yuli Wang,Lihua Jia,Zhonggao Gao
Recently, survivin has been attracting great attention because it plays an important role in inhibiting the apoptosis process of tumor cells. Down-regulating the expression of survivin gene by small interfering RNA (siRNA) offers a promising method for anti-tumor therapy. However, lack of appropriate siRNA delivery vector has significantly hindered the successful application of survivin-targeted siRNA in anti-tumor therapy. The purpose of this study was to use polysaccharide vector TAT-g-CS we synthesized to deliver functional siRNA and evaluate its in vivo anti-tumor activity. TAT-g-CS vector was firstly synthesized and well structurally characterized. MTT assay showed that TAT-g-CS vector exhibited good biocompatibility . TAT-g-CS complexed with siRNA offering nanoparticles with an average particle size of 212.2 nm and a polydispersity index of 0.121, and the zeta potential of the nanoparticles was +18.58 mV. Results from reporter gene assay suggested that luciferase-targeted siRNA when delivered by TAT-g-CS could down-regulate the expression of luciferase gene with 75.3% reduction. Most importantly, we use siRNA Sur targeting survivin gene to assess the in vitro and in vivo delivery capacity of TAT-g-CS and its anti-tumor effects. Our results demonstrated that TAT-g-CS/siRNA Sur nanoparticles not only strongly inhibited the in vitro proliferation of 4T1-Luc tumor cells via inducing cell apoptosis, but also effectively inhibited the in vivo growth and metastasis of malignant breast tumor, which suggested that TAT-g-CS/siRNA nanoparticle was a highly efficient non-viral system for siRNA delivery, especially for anti-tumor therapy based on siRNA therapeutics.
研究领域:
癌症生物学
·
药学
·
纳米技术
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BREAST CANCER RESEARCH AND TREATMENT
·
2018
·Vol. 50
·期 4
·1362-1377
·
IF 3.605
Lai Nar Tung,Senchuan Song,Kin Tak Chan,Mei Yuk Choi,Ho Yu Lam,Chung Man Chan,Zhiyong Chen,Hector K. Wang,Hoi Ting Leung,Simon Law,Yanmin Huang,Huacan Song,Nikki P. Lee
Purpose Tumor xenograft model is an indispensable animal cancer model. In esophageal squamous cell carcinoma (ESCC) research, orthotopic tumor xenograft model establishes tumor xenograft in the animal esophagus, which allows the study of tumorigenesis in its native microenvironment. Materials and Methods In this study,we described two simple and reproducible methods to develop tumor xenograft at the cervical or the abdominal esophagus in nude mice by direct injection of ESCC cells in the esophageal wall. Results In comparing these two methods, the cervical one presented with more clinically relevant features, i.e., esophageal stricture, body weight loss and poor survival. In addition, the derived tumor xenografts accompanied a rapid growth rate and a high tendency to invade into the surrounding structures. This model was subsequently used to study the anti-tumor effect of curcumin, which is known for its potential therapeutic effects in various diseases including cancers, and its analogue SSC-5. SSC-5 was selected among the eight newly synthesized curcumin analogues based on its superior anti-tumor effect demonstrated in an MTT cell proliferation assay and its effects on apoptosis induction and cell cycle arrest in cultured ESCC cells. Treatment of orthotopic tumor-bearing mice with SSC-5 resulted in an inhibition in tumor growth and invasion. Conclusion Taken together, we have established a clinically relevant orthotopic tumor xenograft model that can serve as a preclinical tool for screening new anti-tumor compounds, e.g., SSC-5, in ESCC.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2016
·
IF 2.326
Qin Tang,Fangling Ji,Jianli Guo,Jingyun Wang,Yachen Li,Yongming Bao
Chrysin , one of natural flavonoid compounds, has recently been found to possess anti-inflammatory, antiallergic and anticancer properties. To increase its anticancer effects, 5 chrysin derivates were synthesized on the base of DNA intercalator structure. The inhibiting effects of chrysin and its derivatives on cancer cells Hela, BGC823, MCF-7, HepG2, and normal cells HEK-293, were evaluated by MTT assays . 5-(2′-amino) phenyl-7-cyclohexanemethylchrysin (Ch-1), a unique chrysin derivate, killed all the cancer cells but kept above 60% survival rate in normal cells HEK-293 at 62.5 μM. Treated with chrysin from 250 μM to 500 μM, those cells were still maintained above 60% survival rate. The result of circular dichroism spectra showed that Ch-1 could intercalate DNA while chrysin had no effects on DNA. Interestingly, Hela cells survival rates were 95% and 10%, after treated with 20 μM and 30 μM of Ch-1, respectively. Both intrinsic and extrinsic apoptotic pathway were identified in regulating the cell death caused by Ch-1 in Hela cells. p53, the upstream regulator of apoptotic pathway were extremely significantly up-regulated in Hela cells treated with 25 μM Ch-1. Moreover, the inhibiting effects and apoptotic related proteins responses to Ch-1 on Hela cells were abolished after pre-treated with Pifithrin-α (Pft-α), a p53 inhibitor. So, p53-depedent apoptosis is the crucial factor governing the inhibiting effects of Ch-1 in Hela cells. Amazingly, Ch-1 at non-toxic concentration (2.5–10 μM) enhanced significantly anti-cancer effect of 10-hydroxy camptothecin (HCPT) on Hela, BGC823, and MCF-7 cells.
研究领域:
癌症研究
·
药理学
·
细胞生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Oncotarget
·
2016
·
IF 5.008
Mei Peng,Qiongli Su,Qing Zeng,Le Li,Zhihong Liu,Lei Xue,Yan Cheng,Yanjun Huang,Ting Tao,Hongwei Lv,Xiaohui Li,Xiaojun Tao,Peng Guo,Alex F. Chen,Xiaoping Yang
Anticancer potential of metformin has been extensively studied. However, its anticancer clinical use remains yet to be approved since sufficient concentration on target organs could not be achieved via conventional administration. To overcome this drawback, we aim to examine the efficiency of novel intravesical treatment of metformin on syngeneic orthotopic preclinical model. Three human and one murine bladder cancer cell lines were tested in vitro for inhibitory sensitivity by MTT and cologenic assays. AMPK pathway including AKT, Erk and S6K was examined by western blot and further explored by regulating activated levels using specific inhibitors. In vivo efficacy was determined by Kaplan-Meier survival curves and measurements of body and bladder weights plus tumor biomarkers. Lactic acid and metformin levels of plasma were measured by standard procedures. The results demonstrated that metformin activated AMPK and decreased phosphorylation of Akt and Erk. Furthermore, combinations of metformin with either Akt or Erk inhibitors synergistically diminished cancer proliferation, suggesting the involvement of Akt- and Erk- related pathways. Intravesical metformin 26 and 104 mg/kg, twice per week demonstrated a rapid elimination of the implanted tumor without any evidence of toxicity. In contrast, oral treatment at a dose of 800mg/kg/d exhibited little efficacy whereas severe toxicity existed if the dosage is higher. Collectively, intravesical metformin displays potent inhibition on bladder cancer in vitro and this preclinical study reveals the profound therapeutic application of metformin with durable tolerance via intravesical administration route.
研究领域:
肿瘤学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2023
·
IF 6.6
Tong Li,Dianwei Wang,Zhaopei Guo,Lin Lin,Meng Meng,Cong Liu,Kai Hao,Xuan Pang,Huayu Tian,Xuesi Chen
The emergence of nanocarriers has greatly improved the therapeutic efficacy of chemotherapeutic drugs. As emerging nanocarriers, covalent organic frameworks (COFs) have been increasingly used in biomedicine in recent years. However, due to their inherent chemical stability, existing COF nanocarriers hardly undergo in vivo degradation, which brings potential safety hazards to further applications. In this work, we introduce the azo bond into COFs. When the nanocarrier enters the cell, ˙OH generated by the coordinated Fe response to the H2O2 in the cell will break the azo bond and cause the degradation of the framework structure, accelerating the release of internally loaded DOX to effectively realize tumor treatment. We verified the degradation ability of the materials by constructing model compounds, in vitro drug release, MTT assay and antitumor experiments. Compared with the control groups, the degradable COF accelerates the release of DOX and shows a stronger killing effect on 4T1 cells. Serum biochemical analysis and H&E sections of organs show good biocompatibility for both COFs and degradation products. This work provides a new idea for the design of biodegradable COFs in vivo, and greatly explores the potential application of COF materials in the biomedical field.
研究领域:
纳米技术
·
药学
·
生物医学工程
·
癌症研究
✓ 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）