Revista Brasileira de Farmacognosia-Brazilian Journal of Pharmacognosy
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2024
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IF 1.4
Xie Huilong,Fu Yunrong,Lin Zhisheng,Wang Jiayi,Wu Jingyu,You Xiuhua,Xie Jieming
This study explores the synergistic effect of T-CUS 245C combined with cyclosporin A, and its possible mechanism. T-CUS 245C is an immunotoxin conjugated with tastuzumab and recombinant cucurmosin 245C (CUS 245C ). Cyclosporin A is a calcium antagonist mainly used as an immune-suppressive agent, which enhances the cytotoxicity of immunotoxins through an unknown mechanism. The sulforhodamine B assay, flow cytometry, DNA fragmentation apoptosis assay, and western blot analysis were used to evaluate the synergistic effects of cyclosporin A combined with T-CUS 245C on proliferation inhibition and apoptosis induction in SK-OV-3 ovarian cancer cells with HER-2-overexpressing. Meanwhile, using confocal microscopy and flow cytometry, the effect of cyclosporin A on the intracellular distribution of T-CUS 245C was observed and quantified. The results of this study showed that the combination index of cyclosporin A combined with T-CUS 245C is less than 0.7, indicating that cyclosporin A significantly enhances the proliferation inhibition and apoptosis induction induced by T-CUS 245C in SK-OV-3 cells. The confocal microscopy and flow cytometry results show that cyclosporin A effectively increases the dispersion of T-CUS 245C in the cytoplasm by promoting the endolysosomal escape. This study demonstrates that cyclosporin A combined with T-CUS 245C has a synergistic anticancer effect, by facilitating the release of T-CUS 245C in the intracellular space. Graphical Abstract
研究领域:
肿瘤学
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细胞生物学
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药理学
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DOI
高影响因子
POLYMER TESTING
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2022
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IF 4.931
Ruiling Xu,Junhui Sui,Mingda Zhao,Yuedi Yang,Lei Tong,Yongmei Liu,Yong Sun,Yujiang Fan,Jie Liang,Xingdong Zhang
Human epidermal growth factor receptor-2 (HER-2) positive breast cancer is highly invasive with poor clinical outcomes and high risk of recurrence. Here, trastuzumab functionalized pullulan-doxorubicin nanoparticles (Tz-P-Dox) were developed and characterized as a new anticancer formulation for active targeting HER-2 overexpression of breast cancer cells. The obtained nanoparticles had the hydrodynamic diameter of 66.7 ± 2.0 nm and PDI of 0.218 ± 0.012. And the in vitro results showed significant difference of cell uptake and cytotoxic effect between Tz-P-Dox and non-targeted P-Dox against HER-2 positive cell lines (BT474 and MCF-7 cells). However, the differences between Tz-P-Dox and P-Dox were not observed in HER-2 negative cell lines (MDA-MB-231 cells). These results suggested that trastuzumab functionalized nanoparticles had great potential to be considered as a candidate drug for HER-2 positive breast cancer treatment.
研究领域:
肿瘤学
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药学
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纳米技术
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产品关联
DOI
高影响因子
CHEMICAL PAPERS
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2019
·Vol. 73
·期 6
·1333-1345
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IF 1.246
Jin Shuyu,Sun Xiuyun,Liu Dan,Xie Hua,Rao Yu
The discovery and development of a novel HER-2 tyrosine kinase inhibitor for the treatment of HER2-positive breast cancer are presented in this article. EGFR family has been recognized as a crucial meditator in the cancer progression; HER-2 tyrosine kinase was one of the members among them. In the effort to explore potent HER-2 inhibitors, a novel series of 4-anilino-3-cyanoquinoline derivatives have been designed, synthesized and evaluated. Most compounds possessed modest proliferation inhibition on SK-BR-3 cell line and HER-2 kinase. Compound 16 appeared to be the most potent compound (HER-2 kinase IC 50 : 19.4 nM, SK-BR-3 IC 50 : 94 nM). In the experiment of cellular cytotoxicity assay, compound 16 shows a much lower cytotoxicity than neratinib on Beas-2b cell line (Human bronchial epithelial cells). In conclusion, compound 16 would be a promising lead compound for further anti-breast cancer drug discovery.
研究领域:
药理学
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肿瘤学
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药物化学
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DOI
高影响因子
NANOTECHNOLOGY
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2021
·Vol. 32
·期 42
·425101
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IF 3.874
Qing Zhang,Lian Wu,Shaozheng Liu,Qingjie Chen,Lingpeng Zeng,Xuezhong Chen,Qing Zhang
Photodynamic therapy (PDT) and immunotherapy have been often adopted for ovarian cancer therapy, yet their application is limited by the high recurrence rate and toxic side effects. Intriguingly, nanoparticles contribute to enhancing the performance of PDT. Here, we investigated the synthesis of HER-2-Nanobody (Nb)-conjugated human serum albumin (HSA) incorporated with chlorin (Ce6) and catalase (CAT) (Nb@HCC), and analyzed the synergic effect of Nb@HCC-mediated PDT and immunotherapy for SK-OV-3 tumors. The Ce6 and CAT were incorporated into HSA to construct the HCC nanoparticles. HER-2-Nanobody was the purified bacterial crude extract, and conjugated with HCC to prepare Nb@HCC via heterodisulfide. The effects of Nb@HCC with near infrared ray (NIR) irradiation on moderating hypoxia and hypoxia inducible factor-1α (HIF-1α) expression were evaluated in the SK-OV-3 cells and tumor tissues. A SK-OV-3 tumor-bearing model was developed, where the synergistic effect of Nb@HCC-mediated PDT and anti-CTLA-4 therapy was investigated. Nb@HCC with a 660 nm laser irradiation could induce massive reactive oxygen species and trigger apoptosis in SK-OV-3 cells. Nb@HCC and PDT promoted danger-associated molecular patterns (DAMPs), which indicated immunogenic cell death and maturation of dendritic cells in the SK-OV-3 cells. Irradiated by NIR, Nb@HCC alleviated the hypoxia and decreased the expression of HIF-1α. The Nb@HCC-mediated PDT and anti-CTLA-4 therapy synergically inhibited the progression of distant tumor, and induced T cell infiltration. Biosafety tests suggested that Nb@HCC would not cause damage to the major organs with less toxicity and side effects. To conclude, a combination of Nb@HCC-mediated PDT and anti-CTLA-4 therapy could inhibit the progression of distant tumor to attain remarkable therapeutic outcomes.
研究领域:
肿瘤学
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纳米技术
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免疫治疗
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药学
✓ 已验证
DOI
PubMed
高影响因子
Journal of Biomedical Nanotechnology
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2021
·Vol. 17
·期 8
·1545-1553
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IF 4.099
Xiao Chuanguang,Wang Xiaohong,Shen Jiacheng,Xia Yanjie,Qiu Shusheng,Liang Xiaodong,Gu Wenyue
Despite the broad anticancer activity, whereas the clinical application of luteolin is hindered by unsatisfactory water solubility and non-targeting. Herein, targeted inhibitory effects of luteolin-loading HER2 nanospheres (Her-2-NPs) were successfully prepared by thin film ultrasonic
method. In comparison with the non-targeted nanospheres, Her-2 nanospheres could significantly boost the intake of luteolin in SK-BR-3 cells. The proliferation and apoptosis of breast cancer cells were detected by MTT testing and flow cytometry examination, respectively. Consequently, the
expressions of FOXO1 mRNA level was detected using qPCR assay and protein level was detected using Westernblot. We discovered that Luteolin-loading Her-2 nanospheres could significantly hinder the proliferation of breast cancer cells, down-regulation their migration, and up-regulation FOXO1
expression at mRNA and protein levels, reveal a mechanism whereby luteolin interferes with breast cancer. Collectively, these results suggest Her-2-modified nanospheres increases the efficiency of luteolin uptake and thus improves the treatment benefit of breast cancer.
研究领域:
药学
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肿瘤学
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纳米技术
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分子生物学
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DOI
PubMed
高影响因子
Breast Cancer
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2015
·Vol. 23
·期 3
·445-455
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IF 1.585
Jiang Qiongchao,Hao Shaoyun,Xiao Xiaoyun,Yao Jiyi,Ou Bing,Zhao Zizhuo,Liu Fengtao,Pan Xin,Luo Baoming,Zhi Hui
Background There is an unmet need for specific and sensitive imaging techniques to assess the efficacy of breast cancer therapy, particularly Her-2-expressing cancers. Ultrasonic microbubbles are being developed for use as diagnostic and therapeutic tools. However, nanobubbles circulate longer, are smaller, and diffuse into extravascular tissue to specifically bind target molecules. Here, we characterize a novel Herceptin-conjugated nanobubble for use against Her-2-expressing tumors. Methods Phospholipid-shelled nanobubbles conjugated with Herceptin (NBs-Her) were fabricated using a thin-film hydration method and characterized in vitro in breast cancer cell lines and in vivo in a mouse model. Results The average size of the unconjugated nanobubbles (NBs-Blank) and NBs-Her was 447.1 ± 18.4 and 613.0 ± 25.4 nm, respectively. In cell culture, the NBs-Her adhered to Her-2-positive cells significantly better than to Her-2-negative cells ( p < 0.05). In vivo, the peak intensity and the half-time to washout of the NBs-Her were significantly greater than those of the NBs-Blank ( p < 0.05). In addition, contrast-enhanced ultrasound imaging quality was improved through the use of the NBs-Her. The nanobubbles were able to penetrate into tumor tissue to allow extravascular imaging, but did not penetrate normal skeletal muscle. Conclusions The Herceptin-conjugated nanobubble had many properties that made it useful for in vivo imaging, including longer circulation time and better tumor selectivity. This platform may be able to provide targeted delivery of therapeutic drugs or genes.
研究领域:
肿瘤学
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生物医学工程
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药理学
✓ 已验证
DOI
PubMed
高影响因子
World Journal of Surgical Oncology
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2026
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IF 2.8
Wang Ju,Zhang Yong,Li Heyu,Peng Jikui,Li Haijun,Gao Xiaoping
STIL is a key molecule influencing the proliferation and cell cycle of gastric cancer cells; however, STIL is also expressed in normal tissues. Therefore, designing a drug delivery system that targets gastric cancer cells is crucial for STIL-targeted therapy. In this study, we constructed exosomes targeting the HER-2 receptor and loaded with siSTIL (Anti-HER-2-Exo-siSTIL), and validated the inhibitory effects of Anti-HER-2-Exo-siSTIL on gastric cancer proliferation and metastasis in vivo. Anti-HER-2-Exo-siSTIL was able to enter SGC-7901 cells and inhibit STIL expression, significantly suppressing the growth of SGC-7901 xenograft tumors. By downregulating STIL and the anti-apoptotic protein Bcl-2, and upregulating the pro-apoptotic proteins Bax, Caspase-3, and Caspase-9, Anti-HER-2-Exo-siSTIL effectively induced apoptosis in tumor cells. Furthermore, Anti-HER-2-Exo-siSTIL selectively inhibited lung metastasis of SGC-7901 cells via hematogenous dissemination. In summary, Anti-HER-2-Exo-siSTIL specifically targets and suppresses gastric cancer proliferation and lung metastasis, demonstrating its significant translational potential for gastric cancer therapy.
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产品关联
DOI
高影响因子
International Journal of Pharmaceutics-X
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2024
·
IF 5.2
Xing Liu,Wenwen Shen
In this study, the trastuzumab-functionalized SK-BR-3 cell membrane-wrapped mesoporous silica nanoparticles loaded with pyrotinib (Tra-CM-MSN-PYR) were prepared for targeted therapy of HER2-positive breast cancer. Transmission electron microscopy (TEM) characterization showed that MSN had a spherical morphology with mesoporous channels and that the structure of Tra-CM-MSN was a cell membrane (CM) layer successfully coated on the surface of MSN. A cellular uptake assay demonstrated that FITC-labeled Tra-CM-MSN were taken up by SK-BR-3 breast cancer cells, which illustrated that Tra-CM-MSN had good targeting ability compared with CM-MSN and MSN. In vivo imaging experiments demonstrated significant accumulation of FITC-labeled Tra-CM-MSN in tumor tissues, further proving that Tra-CM-MSN have superior targeting properties. Cell apoptosis experiments suggested that Tra-CM-MSN-PYR significantly inhibited the proliferation of SK-BR-3 breast cancer cells. The results of in vivo animal experiments also showed that Tra-CM-MSN-PYR significantly inhibited tumor growth. These results indicate that Tra-CM-MSN-PYR has potential application as a targeted therapy for HER2-positive breast cancer in the future.
研究领域:
药学
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纳米技术
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肿瘤学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Analytical Methods
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2017
·Vol. 9
·期 17
·2546-2552
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IF 1.9
Weizhe Hong,Gongwei Sun,Yi Zhang,Zhi Xing,Biao Huang,Sichun Zhang,Xinrong Zhang
ICP-MS-based multiplex immunoassays have the advantages of low sample consumption and minimized repetitions of tedious procedures. However, this technique is seldom used in clinical tests because of the complicated matrix effect in clinical samples and the discrimination effect to the target proteins. In this work, we developed an ICP-MS-based magnetic immunoassay by using magnetic beads as highly efficient affinity probes and optimizing the magnetic immunoassay parameters. We applied this method to the simultaneous determination of three crucial gynecological tumor biomarkers that are vital in the prognosis and monitoring of the recurrence of breast cancer and ovarian cancer. The measurable ranges of HER-2, HE4 and CA15-3 were 12–1000 ng mL−1, 8–2000 pmol L−1 and 5–200 U mL−1, with detection limits (3σ) of 3.94 ng mL−1, 2.59 pmol L−1 and 1.62 U mL−1, respectively. The relative standard deviations (RSDs) were 2.61% for HER-2 at 15 ng mL−1, 4.90% for HE4 at 25 pmol L−1 and 6.68% for CA15-3 at 10 U mL−1, indicating good accuracy of the method. The spiking test indicated that the present method had a low matrix effect. Under optimized conditions, the simultaneous detection of HER-2, HE4, and CA15-3 in clinical serum samples was performed and the values correlated well with those obtained by the time resolved fluorescence immunoassay (r2 = 0.9568 for HER-2, 0.9485 for HE4, 0.9133 for CA15-3). The present work shows that the ICP-MS-based magnetic immunoassay meets the requirements for the quantification of three crucial gynecological tumor biomarkers in real clinical tests.
研究领域:
分析化学
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医学诊断
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癌症研究
✓ 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）