College of Health Industry, Zhongshan Torch Polytechnic, Guangdong, China.
Cang Zhou People's Hospital, Cangzhou, China.
J Biomater Appl. 2022 Feb;36(7):1277-1288. doi: 10.1177/08853282211049620. Epub 2021 Oct 24.
Chemotherapeutic agents and photosensitizers often suffer from poor tumor selectivity, high side toxicity, or low water solubility. To address these problems, various drug delivery systems (DDS) have been explored but most of them are toxic, difficult to synthesize, or of single function. In order to design a highly biocompatible, conveniently prepared, multi-functional drug delivery system, herein, an aptamer of vascular endothelial growth factor (VEGF) and a cytosine (C)-DNA fragment were grafted on the surface of superparamagnetic iron oxide nanoparticles (SPION), and then a chemotherapeutic agent daunomycin (DNM) and a photosensitizer 5, 10, 15, 20-tetra (phenyl-4-N-methyl-4-pyridyl) porphyrin (TMPyP) were self-assembled with the hybridized VEGF-based DNA structure. By loading DNM and TMPyP, the DDS displayed strong chemotherapeutic/phototherapeutic capability against cancer cells mechanisms such as mitochondrial dysfunction and ROS elevation, which triggered the apoptosis of the tumor cells. The dual delivery of chemotherapeutical agents and photosensitizers with aptamer/C-rich DNA successfully integrated the functions of pH stimuli-responsive drug release and chemotherapeutic/phototherapeutic modalities into one single system and thus could be considered as an ideal drug delivery vehicle with great potential in clinic.
化疗药物和光敏剂通常存在肿瘤选择性差、毒性高或水溶性低等问题。为了解决这些问题，人们探索了各种药物传递系统（DDS），但大多数都具有毒性、难以合成或具有单一功能。为了设计一种高生物相容性、易于制备、多功能的药物传递系统，本研究将血管内皮生长因子（VEGF）的适体和胞嘧啶（C）-DNA 片段嫁接到超顺磁性氧化铁纳米粒子（SPION）的表面，然后将化疗药物柔红霉素（DNM）和光敏剂 5,10,15,20-四（苯基-4-N-甲基-4-吡啶基）卟啉（TMPyP）与杂交的基于 VEGF 的 DNA 结构自组装。通过装载 DNM 和 TMPyP，该 DDS 对癌细胞表现出强大的化学治疗/光疗能力，其机制包括线粒体功能障碍和 ROS 升高，从而引发肿瘤细胞凋亡。适体/C 富 DNA 的化学治疗药物和光敏剂的双重传递成功地将 pH 刺激响应性药物释放和化学治疗/光疗模式的功能集成到一个单一的系统中，因此可以被认为是一种具有很大临床应用潜力的理想药物传递载体。
