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多金属氧酸盐及其壳聚糖纳米组装体的细胞毒性和酶抑制研究。

Cytotoxicity and enzyme inhibition studies of polyoxometalates and their chitosan nanoassemblies.

作者信息

Shah Hamid Saeed, Al-Oweini Rami, Haider Ali, Kortz Ulrich, Iqbal Jamshed

机构信息

Centre for Advanced Drug Research, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan.

School of Engineering and Science, Jacobs University, P.O. Box 750 561, 28725 Bremen, Germany.

出版信息

Toxicol Rep. 2014 Jun 6;1:341-352. doi: 10.1016/j.toxrep.2014.06.001. eCollection 2014.

Abstract

Polyoxometalates (POMs) have become very significant in biomedical research for their structural diversity which renders them highly active against bacterial, viral and cancer diseases. In this study three different POMs were synthesized and nanoassemblies were made with chitosan (CTS), a natural biodegradable polymer with excellent drug carrier properties. The compounds were tested on two isoenzymes of alkaline phosphatases including tissue specific calf intestine alkaline phosphatase (CIAP) and tissue non-specific alkaline phosphatase (TNAP). Compound [TeWO] (TeW) showed the highest activity (45.4 ± 11.3 nM) among tested compounds against TNAP. Similarly, chitosan-[TeWO] (CTS-TeW) was proved to be a potent inhibitor of CIAP with value of 22 ± 7 nM. A comparative study was made to evaluate their cytotoxic potential against HeLa cells. Among all tested compounds, Chitosan-[NaPWO] (CTS-PW) has showed higher percent cytotoxicity (88 ± 10%) at 10 μM when compared with the standard anticancer drug vincristine (72 ± 7%). The study revealed that selected POMs proved excellent anticancer potential and were equally effective against alkaline phosphatase enzyme, an increased level of which may indicate cancer metastasis.

摘要

多金属氧酸盐(POMs)因其结构多样性在生物医学研究中变得非常重要,这使其对细菌、病毒和癌症疾病具有高度活性。在本研究中,合成了三种不同的POMs,并与壳聚糖(CTS)制成纳米组装体,壳聚糖是一种具有优异药物载体性能的天然可生物降解聚合物。对两种碱性磷酸酶同工酶进行了测试,包括组织特异性小牛肠碱性磷酸酶(CIAP)和组织非特异性碱性磷酸酶(TNAP)。化合物[TeWO](TeW)在测试化合物中对TNAP表现出最高活性(45.4±11.3 nM)。同样,壳聚糖-[TeWO](CTS-TeW)被证明是CIAP的有效抑制剂,其 值为22±7 nM。进行了一项比较研究,以评估它们对HeLa细胞的细胞毒性潜力。在所有测试化合物中,壳聚糖-[NaPWO](CTS-PW)在10 μM时显示出比标准抗癌药物长春新碱(72±7%)更高的细胞毒性百分比(88±10%)。该研究表明,所选的POMs具有优异的抗癌潜力,并且对碱性磷酸酶同样有效,碱性磷酸酶水平升高可能表明癌症转移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/629a/5598103/6efc4f67d0a5/gr1.jpg

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