Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka, 599-8531, Japan.
Macromol Biosci. 2019 Apr;19(4):e1800365. doi: 10.1002/mabi.201800365. Epub 2019 Feb 1.
Sonodynamic therapy (SDT) is a novel promising noninvasive therapy involving utilization of low-intensity ultrasound and sonosensitizer, which can generate reactive oxygen species (ROS) by sonication. In SDT, a high therapeutic effect is achieved by intracellular delivery and accumulation at the target sites of sonosensitizer followed by oxidative damage of produced ROS by sonication. Here, pH- and redox-responsive hollow nanocapsules are prepared through the introduction of disulfide cross-linkages to self-assembled polymer vesicles formed from polyamidoamine dendron-poly(l-lysine) for the efficient delivery of sonosensitizer. As sonosensitizer, doxorubicin (DOX), an anticancer drug accumulating into cell nucleus, is selected. Also, the conjugate of DOX and triphenylphosphonium (TPP-DOX) is synthesized as sonosensitizer with mitochondrial targeting ability. DOX and TPP-DOX are delivered to nucleus and mitochondria by nanocapsules. Furthermore, DOX- or TPP-DOX-loaded nanocapsules exhibit in vitro sonodynamic therapeutic effect to HeLa cells with sonication, which might be through oxidative damage to nucleus and mitochondria.
声动力学疗法（SDT）是一种新的有前途的非侵入性治疗方法，涉及利用低强度超声和声敏剂，通过超声处理产生活性氧（ROS）。在 SDT 中，通过细胞内递送至目标部位并积累声敏剂，然后通过超声处理产生的 ROS 的氧化损伤来实现高治疗效果。在这里，通过引入二硫键交联，制备了 pH 和氧化还原响应的中空纳米胶囊，该纳米胶囊由聚酰胺胺树枝状聚合物-聚（L-赖氨酸）形成的聚合物囊泡自组装而成，用于声敏剂的有效递药。作为声敏剂，选择了阿霉素（DOX），一种积累到细胞核中的抗癌药物。此外，还合成了具有线粒体靶向能力的 DOX 和三苯基膦（TPP-DOX）的轭合物作为声敏剂。纳米胶囊将 DOX 或 TPP-DOX 递送至细胞核和线粒体。此外，DOX 或 TPP-DOX 负载的纳米胶囊在超声处理下对 HeLa 细胞表现出体外声动力学治疗效果，这可能是通过对细胞核和线粒体的氧化损伤。
