Pharmacological and Regulatory Sciences Group (PharmaRegSci), Research Institute for Medicines (iMed.ULisboa), Faculdadde de Farmácia da Universidade de Lisboa, Lisbon, Portugal.
Discipline of Pharmaceutics, School of Pharmacy, University of the Western Cape, Bellville, South Africa.
Pharm Res. 2019 Apr 15;36(6):83. doi: 10.1007/s11095-019-2615-6.
Salinomycin (SAL) is a polyether compound that exhibits strong antimicrobial as well as anticancer activity. Nanomedicine has been at the forefront of drug delivery research with the aim of increasing the efficacy, specificity and reduce toxicity of drugs. There is an intersection between infection and cancer, and cancer patients are prone to bacterial infections. In this study, polymeric micelles were prepared using Pluronic® F127 (PM) to encapsulate SAL (PM_SAL) with the view of enhancing antimicrobial and anticancer activity.
A Quality by Design (QbD) approach was utilized to synthesize PM_SAL, and nanoformulation activity was determined against bacterial (S. aureus, MRSA and E. coli). Effects on cancer cell line A549, i.e. cell viability, prevention of P-gp efflux, vimentin expression, effects on migratory ability of A549 cells. Anticancer activity was determined by ability to eradicate cancer stem-like cells.
PM_SAL demonstrated only efficacy against MRSA, being even higher than that obtained with SAL. In A549 cells, a 15-fold increase in P-gp's expression as well as a significant decrease of the cell's migration, was observed.
PM_SAL can interfere with the oncogenic protein VIM, involved in the crucial mechanisms EMT, downregulating its expression. Altogether data obtained indicates that this antibiotic and the developed polymeric micelle system is a very promising inhibitor of tumor cell growth.
盐霉素（SAL）是一种聚醚化合物，具有很强的抗菌和抗癌活性。纳米医学一直处于药物输送研究的前沿，旨在提高药物的疗效、特异性并降低毒性。感染和癌症之间存在交叉，癌症患者容易发生细菌感染。在这项研究中，使用 Pluronic® F127（PM）制备聚合物胶束以包裹 SAL（PM_SAL），以期增强抗菌和抗癌活性。
采用质量源于设计（QbD）方法合成 PM_SAL，并测定其纳米制剂对细菌（金黄色葡萄球菌、耐甲氧西林金黄色葡萄球菌和大肠杆菌）的活性。研究 PM_SAL 对肺癌细胞系 A549 的影响，包括细胞活力、预防 P-糖蛋白外排、波形蛋白表达以及对 A549 细胞迁移能力的影响。通过消除癌症干细胞样细胞的能力来确定抗癌活性。
PM_SAL 仅对耐甲氧西林金黄色葡萄球菌具有疗效，甚至高于 SAL 的疗效。在 A549 细胞中，观察到 P-糖蛋白表达增加了 15 倍，细胞迁移显著减少。
PM_SAL 可以干扰参与 EMT 关键机制的致癌蛋白 VIM，下调其表达。总之，所获得的数据表明，这种抗生素和开发的聚合物胶束系统是一种非常有前途的肿瘤细胞生长抑制剂。
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