Synthesis, self-assembly and anticancer drug encapsulation and delivery properties of cyclodextrin-based giant amphiphiles
Synthesis, self-assembly and anticancer drug encapsulation and delivery properties of cyclodextrin-based giant amphiphiles
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DOI：
10.1016/j.carbpol.2020.117135
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发表时间：
2021-01-15
影响因子：
11.2
通讯作者：
Cena, Valentin
中科院分区：
文献类型：
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作者：
Gallego-Yerga, Laura;de la Torre, Cristina;Cena, Valentin
可自组装成纳米球或纳米囊泡的环糊精-杯芳烃巨型两亲物能够以>80%的包封率包裹抗癌疏水性药物多西紫杉醇、替莫唑胺和考布他汀A-4并将其递送至肿瘤细胞，从而将其治疗效果提高1-3个数量级。这些两亲物通过插入二硫键进行修饰，赋予它们氧化还原反应性。模仿肿瘤微环境中存在的高谷胱甘肽水平有利于所得纳米化合物的分解和货物释放。负载抗癌药物的纳米制剂抑制前列腺癌、乳腺癌、胶质母细胞瘤、结肠癌或宫颈癌细胞系增殖，IC50值明显低于游离药物观察到的值。细胞周期分析表明载药纳米化合物和游离药物具有相似的作用机制。结果强烈表明，环糊精-杯芳烃异二聚体原型是纳米制剂的优异支架，旨在提供由于肿瘤细胞溶解度低而生物利用度有限的抗癌药物，从而显着提高其有效性。
Cyclodextrin-calixarene giant amphiphiles that can self-assemble into nanospheres or nanovesicles have the ability to encapsulate the anticancer hydrophobic drugs docetaxel, temozolomide and combretastatin A-4 with encapsulation efficiencies >80% and deliver them to tumoral cells, enhancing their therapeutic efficacy by 1-3 orders of magnitude. These amphiphiles were modified by inserting a disulfide bridge confering them redox responsiveness. Disassembly of the resulting nanocompounds and cargo release was favored by high glutathione levels mimicking those present in the tumor microenvironment. Anticancer drug-loaded nanoformulations inhibited prostate, breast, glioblastoma, colon or cervix cancer cell lines proliferation with IC50 values markedly below those observed for the free drugs. Cell-cycle analysis indicated a similar mechanism of action for drugloaded nanocompounds and free drugs. The results strongly suggest that the cyclodextrin-calixarene heterodimer prototype is an excellent scaffold for nanoformulations aimed to deliver anticancer drugs with limited bioavailability due to low solubility to tumoral cells, markedly increasing their effectivity.