School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.
J Mater Chem B. 2019 Dec 7;7(45):7141-7151. doi: 10.1039/c9tb01702j. Epub 2019 Oct 30.
Triple-negative breast cancer (TNBC) is characterized by a high metastatic rate, which can seriously threaten women's health. ROS play an important role in tumor development and metastasis. Excessive ROS can induce tumor cell apoptosis and inhibit tumor cell metastasis. This study investigated Fenton-reaction-stimulative nanoparticles (P@P/H NPs) containing ROS-responsive molecular switches for antitumor metastasis by amplifying the ROS and activating the cascade biological reaction of ROS in tumor cells. Spheroidal P@P/H NPs exhibited a uniform size of 68.18 ± 0.29 nm, high drug cumulative release of 97.59% in response to HO at 24 h, and satisfactory cytotoxicity with the IC value of 0.50 ± 0.02 μg mL. The markedly elevated ROS level caused by P@P/H NPs generated an evident antitumor metastasis effect in vitro by facilitating the expressions of cytochrome c, caspase-9, and caspase-3 and blocking that of matrix metalloprotein 9 (MMP-9). Moreover, P@P/H NPs engendered an excellent tumor inhibition rate of 56.37% and antitumor metastasis effect in vivo. Therefore, P@P/H NPs could respond to HO in tumor cells to rapidly disassemble and further increase the ROS to induce antitumor metastasis via the Fenton reaction.
三阴性乳腺癌（TNBC）的转移率较高，严重威胁着女性的健康。ROS 在肿瘤的发生和转移中起着重要作用。过量的 ROS 可以诱导肿瘤细胞凋亡，抑制肿瘤细胞转移。本研究通过放大 ROS 并激活肿瘤细胞中 ROS 的级联生物反应，探讨了含有 ROS 响应分子开关的芬顿反应刺激纳米颗粒（P@P/H NPs）在抗肿瘤转移中的作用。球形 P@P/H NPs 的粒径为 68.18 ± 0.29nm，在 24 小时内对 HO 的药物累积释放率高达 97.59%，具有令人满意的细胞毒性，IC 值为 0.50 ± 0.02μg/mL。P@P/H NPs 产生的 ROS 水平显著升高，通过促进细胞色素 c、caspase-9 和 caspase-3 的表达并阻断基质金属蛋白酶 9（MMP-9）的表达，在体外产生了明显的抗肿瘤转移作用。此外，P@P/H NPs 在体内产生了高达 56.37%的肿瘤抑制率和抗肿瘤转移作用。因此，P@P/H NPs 可以在肿瘤细胞中对 HO 作出反应，迅速解体，并通过芬顿反应进一步增加 ROS，从而诱导抗肿瘤转移。
