Supramolecular self-associating amphiphiles (SSAs) as nanoscale enhancers of cisplatin anticancer activity.
Supramolecular self-associating amphiphiles (SSAs) as nanoscale enhancers of cisplatin anticancer activity.
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DOI：
10.1039/d1ra02281d
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发表时间：
2021-04-13
期刊：
影响因子：
3.9
通讯作者：
Hiscock JR
中科院分区：
文献类型：
--
作者：
Dora NO;Blackburn E;Boles JE;Williams GT;White LJ;Turner SEG;Hothersall JD;Askwith T;Doolan JA;Mulvihill DP;Garrett MD;Hiscock JR
由于肿瘤细胞渗透效率低，许多化疗药物的治疗窗口较窄。超分子自结合两亲盐（SSAs）是一类独特的小分子，有潜力成为下一代抗癌药物和/或治疗增强剂。在此，我们证明了7种ssa对卵巢和胶质母细胞瘤癌细胞的细胞毒性。我们还利用其中一种先导ssa的固有荧光特性，为这类化合物结合到癌细胞外部表面并渗透到细胞膜上并内化提供证据。此外，我们证明了两种铅SSAs对顺铂介导的卵巢癌细胞毒性的协同作用，并表明这与单独使用任何一种药物增加的DNA损伤和凋亡有关。这项工作提供了第一个证据，证明ssa与癌细胞膜相互作用并渗透，增强化疗药物在人类癌细胞中的细胞毒性活性。在此，我们展示了SSA技术在开发协同下一代抗癌治疗方面的潜力。
Many chemotherapeutic drugs have a narrow therapeutic window due to inefficient tumour cell permeation. Supramolecular self-associating amphiphilic salts (SSAs) are a unique class of small molecules that offer potential as next generation cancer drugs and/or therapeutic enhancement agents. Herein, we demonstrate the cytotoxicity of seven SSAs towards both ovarian and glioblastoma cancer cells. We also utilize the intrinsic fluorescent properties of one of these lead SSAs to provide evidence for this class of compound to both bind to the exterior cancer cell surface and permeate the cell membrane, to become internalized. Furthermore, we demonstrate synergistic effects of two lead SSAs on cisplatin-mediated cytotoxicity of ovarian cancer cells and show that this correlates with increased DNA damage and apoptosis versus either agent alone. This work provides the first evidence that SSAs interact with and permeate cancer cell membranes and enhance the cytotoxic activity of a chemotherapeutic drug in human cancer cells. Herein we show the potential SSA technology towards the development of synergistic next-generation anticancer treatments.
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影响因子：
3.9
作者：
Boles JE;Ellaby RJ;Shepherd HJ;Hiscock JR
通讯作者：
Hiscock JR
影响因子：
78.8
作者：
Cleeland, Charles S.;Allen, Jeff D.;Skillings, Jamey
通讯作者：
Skillings, Jamey
DOI：
10.1002/chem.201801280
发表时间：
2018-05-28
期刊：
Chemistry (Weinheim an der Bergstrasse, Germany)
影响因子：
--
作者：
White LJ;Tyuleva SN;Wilson B;Shepherd HJ;Ng KKL;Holder SJ;Clark ER;Hiscock JR
通讯作者：
Hiscock JR
影响因子：
4.9
作者：
Medina-Carmona, Encarnacion;Varela, Lorena;Ortega-Roldan, Jose L.
通讯作者：
Ortega-Roldan, Jose L.
影响因子：
10.3
作者：
SKEHAN, P;STORENG, R;BOYD, MR
通讯作者：
BOYD, MR