College of Chemistry and Pharmaceutical Engineering, Nanyang Normal University, Nanyang 473061, China.
Molecules. 2024 Aug 22;29(16):3970. doi: 10.3390/molecules29163970.
To synthesize an effective and versatile nano-platform serving as a promising carrier for controlled drug delivery, visible-light-induced diselenide-crosslinked polyurethane micelles were designed and prepared for ROS-triggered on-demand doxorubicin (DOX) release. A rationally designed amphiphilic block copolymer, poly(ethylene glycol)--poly(diselenolane diol-co-isophorone diisocyanate)--poly(ethylene glycol) (PEG--PUSe--PEG), which incorporates dangling diselenolane groups within the hydrophobic PU segments, was initially synthesized through the polycondensation reaction. In aqueous media, this type of amphiphilic block copolymer can self-assemble into micellar aggregates and encapsulate DOX within the micellar core, forming DOX-loaded micelles that are subsequently in situ core-crosslinked by diselenides via a visible-light-triggered metathesis reaction of Se-Se bonds. Compared with the non-crosslinked micelles (NCLMs), the as-prepared diselenide-crosslinked micelles (CLMs) exhibited a smaller particle size and improved colloidal stability. In vitro release studies have demonstrated suppressed drug release behavior for CLMs in physiological conditions, as compared to the NCLMs, whereas a burst release of DOX occurred upon exposure to an oxidation environment. Moreover, MTT assay results have revealed that the crosslinked polyurethane micelles displayed no significant cytotoxicity towards HeLa cells. Cellular uptake analyses have suggested the effective internalization of DOX-loaded crosslinked micelles and DOX release within cancer cells. These findings suggest that this kind of ROS-triggered reversibly crosslinked polyurethane micelles hold significant potential as a ROS-responsive drug delivery system.
为了合成一种有效且多功能的纳米平台，作为控制药物释放的有前途的载体，设计并制备了可见光诱导的二硒键交联的聚氨酯胶束，用于 ROS 触发的阿霉素（DOX）按需释放。通过缩聚反应，最初合成了一种合理设计的两亲性嵌段共聚物，聚（乙二醇）-聚（二硒醇烷二醇-共-异佛尔酮二异氰酸酯）-聚（乙二醇）（PEG-PUse-PEG），其在疏水性 PU 段中包含悬挂的二硒醇基团。在水介质中，这种两亲性嵌段共聚物可以自组装成胶束聚集体，并将 DOX 封装在胶束核内，形成负载 DOX 的胶束，随后通过硒-硒键的可见光引发的复分解反应原位交联。与非交联胶束（NCLMs）相比，所制备的二硒键交联胶束（CLMs）具有更小的粒径和改善的胶体稳定性。体外释放研究表明，与 NCLMs 相比，CLMs 在生理条件下表现出抑制的药物释放行为，而在暴露于氧化环境时会发生 DOX 的爆发释放。此外，MTT 测定结果表明，交联聚氨酯胶束对 HeLa 细胞没有明显的细胞毒性。细胞摄取分析表明，载药交联胶束的有效内化和 DOX 在癌细胞内的释放。这些发现表明，这种 ROS 触发的可还原交联聚氨酯胶束作为一种 ROS 响应性药物传递系统具有重要的应用潜力。
