Department of Breast Surgery, The Second Hospital of Jilin University, Changchun, People's Republic of China.
Int J Nanomedicine. 2022 Mar 5;17:989-1002. doi: 10.2147/IJN.S348618. eCollection 2022.
Sonodynamic therapy (SDT) has rapidly advanced as a promising alternative to conventional photodynamic therapy owing to its preferable therapeutic depth. However, single-modal SDT exhibits limited efficacy due to the long-term hypoxia in tumors.
To address these issues, we proposed a synergistic SDT strategy that integrates mitochondrial targeting with nitric oxide (NO) gas therapy by using multifunctional nanoplatforms. The nanoplatform, which was named as T-mTNPs@L-Arg, was composed of mesoporous titanium dioxide loaded with the NO donor precursor L-arginine (L-Arg) and modified with triphenyl phosphonium (TPP), a mitochondria-targeting ligand. Therefore, T-mTNPs@L-Arg could efficiently concentrate into mitochondria and release NO gas as well as generate reactive oxygen species (ROS) with ultrasound stimulus. Importantly, the released NO gas exerted multiple synergies with SDT, including inducing NO poisoning, generating more lethal reactive nitrogen species (RNS) by reaction with ROS, and alleviating hypoxia through NO-mediated mitochondrial respiration inhibition. On account of the synergistic effects, T-mTNPs@L-Arg showed an outstanding SDT efficacy and a reduced side effect.
This work designed a nanoplatform to integrate mitochondria targeting, SDT and NO gas therapy, providing a new strategy for highly efficient breast cancer therapy.
由于其更好的治疗深度，声动力学疗法（SDT）作为一种有前途的替代传统光动力疗法的方法已经迅速发展。然而，由于肿瘤中长期存在的缺氧，单一模式的 SDT 表现出有限的疗效。
为了解决这些问题，我们提出了一种联合 SDT 策略，通过使用多功能纳米平台将线粒体靶向与一氧化氮（NO）气体治疗相结合。该纳米平台被命名为 T-mTNPs@L-Arg，由负载 NO 供体前体 L-精氨酸（L-Arg）的介孔二氧化钛和一种线粒体靶向配体三苯基膦（TPP）组成。因此，T-mTNPs@L-Arg 可以在超声刺激下高效地聚集到线粒体中，释放 NO 气体，并产生活性氧（ROS）。重要的是，释放的 NO 气体与 SDT 发挥了多种协同作用，包括诱导 NO 中毒、与 ROS 反应生成更致命的活性氮物种（RNS），以及通过 NO 介导的线粒体呼吸抑制缓解缺氧。由于协同作用，T-mTNPs@L-Arg 表现出出色的 SDT 疗效和较低的副作用。
本工作设计了一种纳米平台，将线粒体靶向、SDT 和 NO 气体治疗相结合，为高效乳腺癌治疗提供了一种新策略。
