National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, PR China.
National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, PR China.
Carbohydr Polym. 2023 Jul 1;311:120748. doi: 10.1016/j.carbpol.2023.120748. Epub 2023 Mar 1.
A novel type of diselenide bond-bridged hydroxyethyl starch-doxorubicin conjugate, HES-SeSe-DOX, was synthesized via a specially designed multistep synthetic route. The optimally achieved HES-SeSe-DOX was further combined with photosensitizer, chlorin E6 (Ce6), to self-assemble into HES-SeSe-DOX/Ce6 nanoparticles (NPs) for potentiating chemo-photodynamic anti-tumor therapy via diselenide-triggered cascade actions. HES-SeSe-DOX/Ce6 NPs were observed to disintegrate through the cleavage or oxidation of diselenide-bridged linkages in response to the stimuli arising from glutathione (GSH), hydrogen peroxide and Ce6-induced singlet oxygen, respectively, as evidenced by the enlarged size with irregular shapes and cascade drug release. In vitro cell studies exhibited that HES-SeSe-DOX/Ce6 NPs in combination with laser irradiation effectively consumed intracellular GSH and promoted a large rise in levels of reactive oxygen species in tumor cells, actuating the disruption of intracellular redox balance and the enhanced chemo-photodynamic cytotoxicity against tumor cells. The in vivo investigations revealed that HES-SeSe-DOX/Ce6 NPs were inclined to accumulate in tumors with persistent fluorescence emission, inhibited tumor growth with high efficacy and had good safety. These findings demonstrate the potential of HES-SeSe-DOX/Ce6 NPs for use in chemo-photodynamic tumor therapy and suggest their viability for clinical translation.
一种新型的二硒键桥联羟乙基淀粉-阿霉素缀合物 HES-SeSe-DOX 通过专门设计的多步合成路线合成。最佳合成的 HES-SeSe-DOX 进一步与光敏剂，叶绿素 E6（Ce6）结合，通过二硒键触发级联反应自组装成 HES-SeSe-DOX/Ce6 纳米颗粒（NPs），以增强化学-光动力抗肿瘤治疗。研究表明，HES-SeSe-DOX/Ce6 NPs 通过二硒键桥联键的断裂或氧化而解体，以响应来自谷胱甘肽（GSH）、过氧化氢和 Ce6 诱导的单线态氧的刺激，表现为尺寸增大、形状不规则和级联药物释放。体外细胞研究表明，HES-SeSe-DOX/Ce6 NPs 与激光照射联合使用，可有效消耗细胞内 GSH，并促进肿瘤细胞内活性氧水平的大幅升高，从而破坏细胞内氧化还原平衡，增强对肿瘤细胞的化学-光动力细胞毒性。体内研究表明，HES-SeSe-DOX/Ce6 NPs 倾向于在肿瘤中积累，具有持续的荧光发射，高效抑制肿瘤生长，具有良好的安全性。这些发现表明 HES-SeSe-DOX/Ce6 NPs 具有用于化学-光动力肿瘤治疗的潜力，并表明它们具有临床转化的可行性。
