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链长对负载于 SBA-15 纳米结构二氧化硅的(烷基-ω-醇)三苯基锡(IV)的细胞毒性活性的影响及 SBA-15~Cl|PhSn(CH)OH 的体内研究。

Effect of chain length on the cytotoxic activity of (alkyl-ω-ol)triphenyltin(IV) loaded into SBA-15 nanostructured silica and in vivo study of SBA-15~Cl|PhSn(CH)OH.

机构信息

Institute of Chemistry, Martin Luther University Halle-Wittenberg, Kurt-Mothes-Straße 2, D-06120 Halle, Germany.

Institute for Biological Research "Siniša Stanković"- National Institute of Republic of Serbia, University of Belgrade, Bulevar despota Stefana 142, 11060 Belgrade, Serbia.

出版信息

Biomater Adv. 2022 Sep;140:213054. doi: 10.1016/j.bioadv.2022.213054. Epub 2022 Jul 30.

Abstract

A series of nanostructured SBA-15-based materials functionalized with the tetraorganotin(IV) metallodrugs PhSn(CH)OH (n = 3, 4, 6, 8 and 11) are synthesized and structurally characterized by different techniques used in solid-state chemistry. The cytotoxicity of both the organotin(IV) compounds and the tin-functionalized SBA-15 materials are studied against different cancer cell lines observing that the materials have similar cytotoxic activity in comparison with the free organotin compounds in terms of mass. However, considering that the percentage of active metal compound loaded into material is low, the utilization of mesoporous silica as drug vehicle clearly improves the cytotoxic effectiveness of metal-based drugs against cancer cells. One of the most potent between all tested systems is material SBA-15Cl|PhSn(CH)OH. Its cytotoxicity seems to come from additional mechanisms apart from apoptosis provoking cell reprogram in B16 melanoma into more mature and less aggressive phenotype. Moderated production of ROS/RNS is probably in the background of observed phenomenon. Obtained results are further confirmed in syngeneic mouse model of melanoma in C57BL6 mice. The in vivo results show that SBA-15 do not disturb tumor growth, while both PhSn(CH)OH and SBA-15Cl|PhSn(CH)OH significantly decreases tumor volume with an enhancement of the antitumor potential of the tetraorganotin(IV) compound upon immobilization in SBA-15.

摘要

一系列基于纳米结构 SBA-15 的材料被合成出来,并通过固态化学中使用的不同技术进行了结构表征,这些材料用四有机锡(IV)金属药物 PhSn(CH)OH(n=3、4、6、8 和 11)进行了功能化。研究了两种有机锡(IV)化合物和锡功能化 SBA-15 材料对不同癌细胞系的细胞毒性,观察到在质量方面,与游离有机锡化合物相比,这些材料具有相似的细胞毒性活性。然而,考虑到负载到材料中的活性金属化合物的百分比较低,介孔硅作为药物载体的使用明显提高了金属基药物对癌细胞的细胞毒性效果。在所有测试系统中,最有效的是 SBA-15Cl|PhSn(CH)OH 材料。其细胞毒性似乎来自于除凋亡以外的额外机制,促使 B16 黑色素瘤细胞重新编程为更成熟、侵袭性更小的表型。观察到的现象可能与 ROS/RNS 的适度产生有关。在 C57BL6 小鼠的黑色素瘤同种异体小鼠模型中进一步证实了获得的结果。体内结果表明 SBA-15 不会干扰肿瘤生长,而 PhSn(CH)OH 和 SBA-15Cl|PhSn(CH)OH 都能显著降低肿瘤体积,同时增强了四有机锡(IV)化合物在 SBA-15 中的固定化的抗肿瘤潜力。

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