Mitochondria-targeted high-load sound-sensitive micelles for sonodynamic therapy to treat triple-negative breast cancer and inhibit metastasis
Mitochondria-targeted high-load sound-sensitive micelles for sonodynamic therapy to treat triple-negative breast cancer and inhibit metastasis
复制标题
DOI：
10.1016/j.msec.2021.112054
复制
发表时间：
2021-03-27
影响因子：
7.9
通讯作者：
Jiang, Zhenqi
中科院分区：
文献类型：
--
作者：
Han, Xiao;Song, Zeyu;Jiang, Zhenqi
乳腺癌是全球女性最常见的癌症，其中10？20%占三阴性乳腺癌（TNBC）。与其他类型的乳腺癌相比，TNBC更具侵袭性，缺乏有效的治疗靶点，转移率更高。这些特征导致TNBC患者的治疗和预后不良。声动力学疗法（SDT）是一种新兴的非侵入性手术，具有高组织穿透性，可治疗癌症。因此，我们设计了一种用于SDT的新型声敏剂PEGIR780@Ce6，其在抑制癌细胞并同时抑制癌细胞的迁移和侵袭方面表现出优异的性能。体外和体内实验表明，PEGIR780@Ce6作为声敏剂可以产生比IR 780和游离Ce 6单独更高水平的活性氧（ROS），从而产生更好的抗癌效果。此外，PEG-IR 780 @ Ce 6在体外和体内均抑制MDA-MB-231细胞的迁移和侵袭，表明其可以抑制TNBC的转移。此外，PEG-IR 780 @ Ce 6的长循环时间和肿瘤靶向能力保证了其在肿瘤中的积累。此外，体外和体内实验均表明PEG-IR 780 @ Ce 6的生物相容性和生物安全性。总之，我们的结果共同表明，新设计的声敏剂PEG-IR 780 @ Ce 6是一种有前途的TNBC治疗选择，具有优异的治疗效果和低副作用。
Breast cancer is the most common cancer among women worldwide, of which 10?20% accounts for triplenegative breast cancer (TNBC). TNBC is more aggressive, lacks an effective treatment target, and has a higher metastasis rate compared to other types of breast cancers. These characteristics result in poor therapeutic and prognostic outcomes in patients with TNBC. Sonodynamic therapy (SDT) is an emerging non-invasive procedure with high-tissue penetration properties to treat cancer. Therefore, we designed a new sonosensitizer, PEGIR780@Ce6 for SDT, which showed excellent performance in inhibiting cancer cells and in simultaneously suppressing the migration and invasion of cancer cells. In vitro and in vivo experiments showed that PEGIR780@Ce6 as a sonosensitizer could generate higher levels of reactive oxygen species (ROS) than IR780 and free Ce6 alone, thereby resulting in better anti-cancer effects. Besides, PEG-IR780@Ce6 inhibited the migration and invasion of MDA-MB-231 cells, both in vitro and in vivo, which indicated that it could suppress the metastasis of TNBC. Moreover, the long circulation time and the mitochondria-targeting ability of PEG-IR780@Ce6 guaranteed its accumulation in the tumor. In addition, both in vitro and in vivo experiments indicated the biocompatibility and biosafety of PEG-IR780@Ce6. In conclusion, our results collectively suggested that the newly designed sonosensitizer, PEG-IR780@Ce6, is a promising treatment option for TNBC with excellent therapeutic effects and low side effects.