Biodegradable multiblock polyurethane micelles with tunable reduction-sensitivity for on-demand intracellular drug delivery
Biodegradable multiblock polyurethane micelles with tunable reduction-sensitivity for on-demand intracellular drug delivery
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DOI：
10.1039/c4ra01478b
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发表时间：
2014-06
期刊：
影响因子：
3.9
通讯作者：
Xueling He;Mingming Ding;Jiehua Li;Hong Tan;Q. Fu;Liang Li
中科院分区：
文献类型：
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作者：
Xueling He;Mingming Ding;Jiehua Li;Hong Tan;Q. Fu;Liang Li
含有二硫键的氧化还原响应型纳米载体在靶向细胞内药物传递方面特别有希望。然而，传统的还原敏感型纳米载体由于其较差的结构可调整性，通常缺乏对刺激响应的控制。在这项研究中，我们开发了一类可生物降解的多嵌段聚氨酯，其主链上含有不同数量的二硫键。这种可还原的聚氨酯显示出有趣的相行为和自组装特性，以及在模拟细胞内还原的环境下触发释放曲线。研究发现，氧化还原敏感的聚氨酯胶束可以快速进入肿瘤细胞，并有效地将包裹的有效载荷输送到胞浆中。体外细胞毒性研究表明，紫杉醇聚氨酯胶束能有效抑制肿瘤细胞的增殖，其抑制作用可通过调节聚合物骨架中二硫键的含量来控制。此外，无药物纳米胶束对癌细胞和健康细胞都具有良好的细胞相容性。这些多嵌段生物响应性聚氨酯在进一步开发可控的细胞内药物转运体方面具有很大的前景。
Redox-responsive nanovehicles containing disulfide bonds are particularly promising for targeted intracellular drug delivery. However, conventional reduction-sensitive nanocarriers generally lack control of stimuli-responsiveness due to their poor structural tunability. In this study, we developed a class of biodegradable multiblock polyurethanes bearing varied amounts of disulfide linkages in their backbone. The reducible polyurethanes exhibit interesting phase behavior and self-assembly properties, as well as triggered release profiles under an intracellular reduction-mimicking environment. It was found that the redox-sensitive polyurethane micelles can rapidly enter tumor cells and efficiently transport the encapsulated payloads into the cytosol. In vitro cytotoxicity studies demonstrated that the paclitaxel-loaded polyurethane micelles could inhibit the proliferation of tumor cells effectively, with the inhibition effects controlled by adjusting the disulfide content in the polymeric backbone. In addition, the drug-free nanomicelles possess good cytocompatibility toward both cancer cells and healthy cells. These multiblock bioresponsive polyurethanes hold great promise in the further development of controllable intracellular drug transporters.