Advanced Healthcare Materials
·
2018
·Vol. 7
·期 22
·1800830
·
IF 5.609
Li Song,Xinghua Dong,Shuang Zhu,Chunfang Zhang,Wenyan Yin,Xiao Zhang,Xiangfeng Liu,Zhanjun Gu
Although various types of photothermal agents are developed for photothermal cancer therapy, relatively few photothermal agents exhibit high tumor inhibition rate under relatively mild conditions. Herein, a multifunctional Bi 2 S 3 –Tween 20 nanoplatform loaded with PI3K inhibitor LY294002 is designed as a novel photothermal agent for inhibitor and photothermal synergistic therapy of tumors under mild photothermal therapy conditions. The LY294002 of PI3K inhibitor, after being loaded by Bi 2 S 3 –Tween 20 nanodots, exhibits greatly increased drug utilization and reduced side effects on normal tissues. In vivo, Bi 2 S 3 –Tween 20@LY294002 upon near-infrared 808 nm laser irradiation shows potent antitumor activity under relatively mild conditions (power density: 0.6 W cm −2 ). Moreover, the mechanism studies also demonstrate that Bi 2 S 3 –Tween 20@LY294002 potently kills LoVo cancer cells under low-power near-infrared light irradiation, by downregulating the expression of heat shock protein 70 (HSP70) so as to increase the sensitivity of tumor cell hyperthermia and activating BAX/BAK-regulated mitochondrial apoptosis pathway. The results demonstrate that the newly synthesized multifunctional nanoplatform paves a new avenue for accurate therapy of photothermal-resistant cancer.
研究领域:
纳米技术
·
癌症治疗
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药学科学
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CHEMICAL RESEARCH
·
2022
·
IF 1.097
Tiandi Ding,HaiJiao Chen,Yan Li,Ying Li,Ying Zhi,Zhiqiang Qu,Qiang Sun,Qingqiang Yao,Bo Liu
Sphingosine kinase is a lipid kinase that catalyzes the phosphorylation of sphingosine to sphingosine-1-phosphate. Sphingosine-1-phosphate is a bioactive lipid that regulates biological processes. The overexpression of sphingosine kinases is related to a variety of pathophysiological conditions. For example, SphK1 has been shown to be highly expressed in various cancer cells including ovarian, cervical, colon, stomach, lung, and brain cancer. Inhibition of sphingosine kinases is a promising way to treat diseases such as cancer. Through computer-aided drug design, we have discovered a new SphK1 inhibitor named Amb30572637 (SAMS10). In this report, we describe the discovery process and biological characteristics. In biochemical experiments, SAMS10 shows a prominent inhibitory effect on SphK1, with an IC50 value of 9.8 μM. Subsequent MTT experiments show that SAMS10 has anticancer effects toward A549, SKVO3, A375, and LOVO cell lines and has essentially no cytotoxicity against the healthy cell L929. SAMS10 has significant inhibitory activity against the A549 and LOVO cell lines, with IC50 values of 14.64 and 14.48 μM, respectively. It belongs to a moderately active SphK1 inhibitor with lower anticancer activity than the control compound cisplatin, but the effect of SAMS10 toward SphK1 and its anticancer activity indicate that it is a promising lead compound for the development of effective SphK1 anticancer inhibitors.
研究领域:
药理学
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癌症研究
·
药物发现
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生物化学
·
分子生物学
✓ 已验证
DOI
高影响因子
DRUG DELIVERY
·
2018
·
IF 3.095
Yimeng Zhou,Ning Li,Zhixia Qiu,Xiaoyu Lu,Min Fang,Xijing Chen,Lili Ren,Guangji Wang,Pingkai Ouyang
Triacontanol (TA, C30H62O), abundantly present in plant cuticle waxes and bee waxes, has been found to display promising anti-neoplastic potentials. As a long chain fatty alcohol, TA possesses limited aqueous solubility, which hinders its medicinal application. To overcome its solubility barrier, a polymer prodrug was synthesized through attaching TA to poly ethylene glycol (PEG), using succinic acid as a linker with bifunctional amide and ester bonds. Anti-neoplastic effects of PEG-TA were assessed in LoVo and MCF7 cells, anti-proliferative and apoptosis-inducing activities were subsequently confirmed in mouse xenograft model. Encouragingly, PEG-TA possessed selective anti-cancer ability. It did not exhibit significant cytotoxicity on normal cells. Mechanistic examination revealed inhibition of NF-κB nuclear translocation, suppression on matrix degradation enzyme and down-regulation of angiogenic signaling might contribute to its anti-malignant effects. Pharmacokinetics clearly indicated PEGylated TA (named as mPEG2K-SA-TA) substantially enhanced TA delivery with increased plasma exposure (19,791 vs. 336.25 ng·mL−1·h−1, p < .001), mean residence time (8.46 vs. 2.95 h, p < .001) and elimination half-life (7.78 vs. 2.57 h, p < .001) compared to those of original TA. Moreover, mPEG2K-SA-TA appeared to be safe in preliminary toxicological assessment. PEGylated TA also emerged as a functional carrier to deliver hydrophobic chemotherapeutic agents, since it readily self-assembled to micelles in aqueous solution with a low critical micelle concentration (CMC, 19.1 µg·mL−1). Conclusively, PEG-TA conjugate displayed superior anti-neoplastic activities and low toxicity, as well as facilitated the delivery of other hydrophobic agents, which appeared to be an innovative strategy for cancer therapy.
研究领域:
药理学
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肿瘤学
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药物递送系统
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生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
Biomedical Materials
·
2023
·Vol. 18
·期 4
·045027
·
IF 4
Xiying Fan,Xinying Peng,Tingting Wang,Yi Gu,Guochuan Sun,Qinghui Shou,Haipeng Song,Rui Nian,Wenshuai Liu
This work aimed to establish a simple and feasible method to obtain silk fibroin nanoparticles (SFNPs) with uniform particles size, and then modify the SFNPs with nanobody (Nb) 11C12 targeting the proximal membrane end of carcinoembryonic antigen on the surface of colorectal cancer (CRC) cells. The regenerated silk fibroin (SF) was isolated using ultrafiltration tubes with a 50 kDa molecular weight cut-off, and the retention fraction (named as SF > 50 kDa) was further self-assembled into SFNPs by ethanol induction. Scanning electron microscope (SEM) and high-resolution transmission electron microscop showed that the SFNPs with uniform particles size were formed. Due to electrostatic adsorption and pH responsiveness, SFNPs have been proved to effectively load and release the anticancer drug doxorubicin hydrochloride (DOX) (DOX@SFNPs). Further, targeting molecule Nb 11C12 was used to modify these nanoparticles, constituting the targeted outer layer of the drug delivery system (DOX@SFNPs-11C12), achieving precise localization to cancer cells. The release amount of DOX observed from in vitro drug release profiles increased as follows: pH 7.4 < pH 6.8 < pH 5.4, demonstrating that the DOX release could be accelerated in a weakly acidic environment. In vitro cytotoxicity experiments displayed that SFNPs-11C12 nanoparticles exhibited good safety and biocompatibility. Drug-loaded nanoparticles, DOX@SFNPs-11C12, led to higher LoVo cells apoptosis compared to DOX@SFNPs. Fluorescence spectrophotometer characterization and confocal laser scanning microscopy further showed that the internalization of DOX was highest in the DOX@SFNPs-11C12, certifying that the introduced targeting molecule enhanced the uptake of drug delivery system by LoVo cells. This study provides a simple and operational approach to developing an optimized SFNPs drug delivery system modified by targeting Nb, which can be a good candidate for CRC therapy.
研究领域:
纳米技术
·
癌症研究
·
药物递送系统
·
生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
OncoTargets and Therapy
·
2020
·
IF 3.337
Xia Tian,Meng Liu,Xiaodong Huang,Qingxi Zhu,Weijie Liu,Wei Chen,Yanli Zou,Yishan Cai,Shasha Huang,Aifang Chen,Ting Zhan,Min Huang,Xiaoli Chen,Zheng Han,Jie Tan
Background Noscapine is an opium alkaloid that has recently been shown to potentiate anti-cancer therapeutic effects by inducing apoptosis in various malignant cells without any detectable toxicity. However, the mechanism by which noscapine induces apoptosis in colon cancer cells remains unclear. Materials and Methods In this study, we explored the anti-cancer activity of noscapine in 5-fluorouracil (5-FU)-resistant human colon cancer cell lines HT29/5-FU and LoVo/5-FU and investigated the possible underlying mechanism. The apoptosis and mitochondrial morphology of cells were detected by TUNEL assay and transmission electron microscopy (TEM). The mitochondrial membrane potential (MMP) was determined using JC-1. The mitochondrial permeability transition pore (mPTP) opening was detected by the calcein-AM/cobalt assay. The levels of glucose, lactic, and ATP in cells were evaluated by ELISA kits. Relative protein expression levels were detected by Western blot. Results We verified that PTEN was involved in noscapine-induced apoptosis in HT29/5-FU and LoVo/5-FU cells. Noscapine greatly increased mitochondrial damage by altering mitochondrial morphology, inducing mitochondrial membrane potential depolarization, and enabling mitochondrial permeability transition pore opening in HT29/5-FU and LoVo/5-FU cells. In addition, noscapine inhibited the Warburg effect by decreasing the levels of glucose, lactic acid, and ATP and inhibiting the protein expression of glucose transporter 1, lactate dehydrogenase-B, hexokinase 2, and pyruvate kinase M2 in HT29/5-FU and LoVo/5-FU cells. However, PTEN interference counteracted the effect of noscapine on mitochondrial damage and the Warburg effect in HT29/5-FU and LoVo/5-FU cells by decreasing the activation of PI3K/mTOR signaling. Conclusion These results indicated that noscapine induced the apoptosis of HT29/5-FU and LoVo/5-FU human colon cancer cells by regulating mitochondria damage and the Warburg effect via PTEN, and the process is closely related to the PI3K/mTOR signaling pathway.
研究领域:
肿瘤学
·
细胞生物学
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药理学
·
癌症生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMBIOCHEM
·
2018
·Vol. 19
·期 10
·1060-1065
·
IF 2.774
Xueyu Zhao,Gaochao Lv,Ying Peng,Qingzhu Liu,Xi Li,Shanshan Wang,Ke Li,Ling Qiu,Jianguo Lin
Graphical Active duty : An activatable fluorescent probe consisting of a peptide, Arg-Val-Arg-Arg (RVRR), and an aminoluciferin fluorophore is designed and prepared for the responsive and activatable detection of furin activity in living cells. This probe is shown to have “off–on” florescence properties, and in the presence of furin in vitro, its fluorescence intensity is increased by a factor of ≈3.58. Furin, a protein convertase, plays a crucial role in the progression of tumors. In this work, a new fluorescent probe consisting of a peptide, Arg-Val-Arg-Arg (RVRR), and an aminoluciferin fluorophore was designed and prepared for the responsive and activatable detection of furin activity in vitro and in living cells. We demonstrated that this probe could be responsive toward furin with an “off–on” florescence signal and generated an approximately 3.58-fold enhancement in the fluorescence intensity in vitro. Fluorescence imaging in MDA-MB-468 and LoVo cells showed that the probe could be cleaved by overexpressed furin with fluorescence turn-on in MDA-MB-468 cells, and this probe was also found to be capable of discriminating between furin-overexpressing and furin-deficient cell lines. Our research indicates that this probe has great potential for the detection of furin activity in living cells.
研究领域:
生物化学
·
分子生物学
·
癌症研究
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Immunology
·
2023
·
IF 7.3
Ben Yi,Shuai Zhang,Suying Yan,Yanfei Liu,Zhiqiang Feng,Tianhao Chu,Jun Liu,Wei Wang,Jun Xue,Chunze Zhang,Yijia Wang
Introduction Tumor-infiltrating T lymphocytes in the tumor microenvironment are critical factors influencing the prognosis and chemotherapy outcomes. As a Chinese herbal medicine, Marsdenia tenacissima extract (MTE) has been widely used to treat cancer in China. Its immunoregulatory effects on tumor-associated macrophages is well known, but whether it regulates tumor-infiltrating T-cell functions remains unclear. Method We collected 17 tumor samples from MTE-administered colorectal cancer patients, 13 of which showed upregulation of CD3+/CD8+ tumor-infiltrating T cells. Further in vitro and in vivo experiments were performed to investigate the regulatory effects of MTE on tumor-infiltrating T cells and immune escape of tumors. Results Under single and co-culture conditions, MTE inhibited TGF-β1 and PD-L1 expression in the colorectal cancer (CRC) cell lines HCT116 and LoVo. In Jurkat cells, MTE inhibited FOXP3 and IL-10 expression, increased IL-2 expression, but had no effect on PD-1 expression. These findings were confirmed in vitro using subcutaneous and colitis-associated CRC mouse models. MTE also increased the density of CD3+/CD8+ tumor-infiltrating T cells and exhibited considerable tumor-suppressive effects in these two tumor mouse models. Conclusions Our findings suggested that MTE inhibits the immune escape of cancer cells, a precipitating factor increasing the immune response of T lymphocytes.
研究领域:
肿瘤学
·
免疫学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cancer Medicine
·
2021
·Vol. 10
·期 10
·3358-3372
·
IF 4.452
Dingsheng Liu,Chunsheng Chen,Mingming Cui,Hong Zhang
Recent studies have identified microRNAs (miRNAs) as a compelling novel class of biomarker in colorectal cancer (CRC) development and metastasis. Here, we demonstrated that the level of plasma exosomal miR-140-3p in CRC patients was lower than that in healthy controls. The decreased miR-140-3p level was also observed in CRC patients with liver metastasis. The expression of miR-140-3p in CRC tissues were significantly lower than that in matched normal tissues. Functionally, miR-140-3p overexpression suppressed proliferation, migration, invasion, and β-catenin nuclear translocation, as well as promoted apoptosis in LoVo cells, while inhibition of miR-140-3p reversed these cellular processes in HCT 116 cells. Notably, BCL9 and BCL2 were recognized as direct targets of miR-140-3p. BCL9 knockdown abrogated miR-140-3p inhibitor-induced effects on HCT 116 cells with decreased proliferation, migration, and invasion. BCL2 knockdown increased apoptosis of miR-140-3p inhibitor-transfected HCT 116 cells. In vivo experiments revealed that miR-140-3p overexpression inhibited tumor growth in LoVo xenograft model and diminished metastatic nodules in nude mice liver. Taken together, this work supports that miR-140-3p exerts as a tumor suppressor in CRC progression via targeting BCL9 and BCL2, and suggests miR-140-3p-BCL9/BCL2 axis may be applied in miRNA-based therapy and prognostication of CRC.
研究领域:
肿瘤学
·
分子生物学
·
癌症生物学
·
遗传学
✓ 已验证
DOI
PubMed
高影响因子
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