Yu Jingmou, Liu Mengqi, Zhang Chao, Cheng Lizhen, Peng Changchun, Jiang Dengzhao, Liu Wenbo, Jin Hongguang, Ren Jin
Huzhou Key Laboratory of Medical and Environmental Applications Technologies, School of Life Sciences, Huzhou University, Huzhou, Zhejiang, China.
School of Pharmacy and Life Sciences, Jiujiang University, Jiujiang, Jiangxi, China.
Pharm Dev Technol. 2024 Nov;29(9):945-954. doi: 10.1080/10837450.2024.2411027. Epub 2024 Sep 30.
Herein, we designed and synthesized novel reactive oxygen species (ROS)-responsive glycol chitosan-doxorubicin (DOX) prodrug a ROS-cleavable thioketal (TK) linker. The obtained GC-TK-DOX formed self-assembled nanoparticles of 312 nm in aqueous media. Photosensitizers zinc phthalocyanine (ZnPc)-loaded GC-TK-DOX (GC-TK-DOX/ZnPc) nanoparticles were fabricated by using a dialysis approach. The GC-TK-DOX and GC-TK-DOX/ZnPc nanoparticles were nearly spherical by transmission electron microscopy (TEM) observation. Under 660-nm laser irradiation, GC-TK-DOX/ZnPc could generate singlet oxygen. Further, GC-TK-DOX/ZnPc nanoparticles exhibited ROS-sensitive release of DOX and ZnPc . GC-TK-DOX/ZnPc with laser irradiation showed more drug uptake and higher cytotoxic effects than GC-TK-DOX/ZnPc without irradiation, free DOX and GC-TK-DOX in HeLa tumor cells. Overall, these findings suggested that GC-TK-DOX/ZnPc could be a promising nanoarchitecture for synergetic chemo-photodynamic therapy against tumors.
在此，我们设计并合成了新型活性氧（ROS）响应性壳聚糖-阿霉素（DOX）前药——一种ROS可裂解的硫代缩酮（TK）连接体。所得到的GC-TK-DOX在水性介质中形成了312nm的自组装纳米颗粒。通过透析法制备了负载光敏剂酞菁锌（ZnPc）的GC-TK-DOX（GC-TK-DOX/ZnPc）纳米颗粒。通过透射电子显微镜（TEM）观察，GC-TK-DOX和GC-TK-DOX/ZnPc纳米颗粒近乎球形。在660nm激光照射下，GC-TK-DOX/ZnPc能够产生单线态氧。此外，GC-TK-DOX/ZnPc纳米颗粒表现出对DOX和ZnPc的ROS敏感释放。与未照射的GC-TK-DOX/ZnPc、游离DOX和GC-TK-DOX相比，经激光照射的GC-TK-DOX/ZnPc在HeLa肿瘤细胞中表现出更多的药物摄取和更高的细胞毒性作用。总体而言，这些发现表明GC-TK-DOX/ZnPc可能是一种有前景的纳米结构，用于协同化疗-光动力疗法治疗肿瘤。
