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新型纳米阴离子线性球形树枝状大分子 G2-环丙沙星缀合物的合成与评价及其对前列腺癌的作用。

Synthesis and evaluation of a novel nanosized anionic linear globular dendrimer G2-ciprofloxacin conjugate against prostate cancer.

机构信息

Department of Microbiology, Islamic Azad University, Tehran North Branch, Tehran, Iran.

Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Pak J Pharm Sci. 2020 Nov;33(6):2589-2594.

Abstract

Prostate cancer is the second most common cancer in the world and the fifth cause of cancer deaths in men. Ciprofloxacin enables the inhabitation of the development of prostate cancer. In this regard, we plan to improve the anticancer effect of ciprofloxacin using the anionic G2 dendrimer in conjunction with ciprofloxacin. In the current study, we measured the size and the zeta potential as well as LC Mass to prove the fact that the conjugation was synthesized correctly. The anticancer activity among three groups including Ciprofloxacin, Ciprofloxacin -G2 dendrimer, and control was measured in vitro. In vitro studies showed that G2 anionic linear-globular polyethylene-glycol-based dendrimer, which conjugated to ciprofloxacin, was able to significantly improve the treatment efficacy over clinical ciprofloxacin alone with respect to proliferation assay. Maximal inhibitory concentration (IC) was calculated as 200 μ/mL for ciprofloxacin alone and 30μ/mL for ciprofloxacin-G2 dendrimer. In addition, the growth of DU-145 cancerous cells was inhibited by ciprofloxacin-G2 dendrimer conjugate and the number of apoptotic and necrotic cells was increased significantly as evaluated by an annexin V-fluorescein isothiocyanate assay. Ciprofloxacin -G2 dendrimer conjugate was able to increase Bcl-2/Bax ratio in a large scale as compared with the control group and CBL alone. According to the above results, this compound could be considered as a good candidate for functional cancer treatment with low side effects.

摘要

前列腺癌是全球第二大常见癌症,也是男性癌症死亡的第五大原因。环丙沙星能够抑制前列腺癌的发展。在这方面,我们计划使用阴离子 G2 树枝状大分子与环丙沙星结合来提高环丙沙星的抗癌效果。在本研究中,我们测量了大小和 Zeta 电位以及 LC Mass,以证明接枝合成正确的事实。我们测量了包括环丙沙星、环丙沙星-G2 树枝状大分子和对照组在内的三组的体外抗癌活性。体外研究表明,与临床使用的环丙沙星单独相比,连接到环丙沙星的阴离子线性-球形聚乙二醇基树枝状大分子 G2 能够显著提高治疗效果,增殖试验。单独使用环丙沙星的最大抑制浓度(IC)为 200μ/ml,而使用环丙沙星-G2 树枝状大分子的 IC 为 30μ/ml。此外,用环丙沙星-G2 树枝状大分子缀合物抑制 DU-145 癌细胞的生长,并通过 Annexin V-荧光素异硫氰酸盐测定法显著增加凋亡和坏死细胞的数量。与对照组和 CBL 单独相比,环丙沙星-G2 树枝状大分子缀合物能够大规模增加 Bcl-2/Bax 比值。根据上述结果,该化合物可被视为具有低副作用的功能性癌症治疗的良好候选物。

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