ROS Responsive Nanoparticles Encapsulated with Natural Medicine Remodel Autophagy Homeostasis in Breast Cancer,ACS Applied Materials & Interfaces

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ROS Responsive Nanoparticles Encapsulated with Natural Medicine Remodel Autophagy Homeostasis in Breast Cancer
ACS Applied Materials & Interfaces ( IF 8.3 ) Pub Date : 2023-06-14 , DOI: 10.1021/acsami.3c03068
Xinhui Zhang ₁ , Heqi Gao ₂ , Daohe Wei ₁ , Xiaoying Pei ₁ , Yue Zhang ₁ , Jian Wang ₁ , Dan Ding ₂ , Jin Chang ₁ , Xiaoli Wu ₁

Affiliation

In photodynamic therapy (PDT), elevated reactive oxygen species (ROS) activate tumor cell protective autophagy, therefore attenuating the antitumor function of therapy. Hence, inhibition of protective autophagy in tumors can improve the antitumor effect of PDT. Herein, an innovative nanotraditional Chinese medicine system ((TP+A)@TkPEG NPs), which remodeled autophagy homeostasis, was fabricated. A photosensitizer aggregation inducing emission (AIE) and autophagy modulator triptolide (TP, an active ingredient of Tripterygium wilfordii Hook F) were encapsulated into ROS-responsive nanoparticles to improve antitumor effect of PDT in treatment of triple negative breast cancer. We proved that (TP+A)@TkPEG NPs effectively elevated intracellular ROS levels, activated ROS-responsive release of TP and inhibited the proliferation of 4T1 cells in vitro. More importantly, it sharply reduced autophagy related genes transcription and proteins expression in 4T1 cells, then promote cell apoptosis. In addition, this nanoherb therapeutic system effectively orientated to tumor sites, achieved efficient inhibition of tumor, and extended the survival time of 4T1-bearing mice in vivo. Further results confirmed that (TP+A)@TkPEG NPs remarkably inhibit the expression level of autophagy related initiation gene (becline-1) and elongation protein (light chain 3B) in tumor microenvironment and then block PDT induced protective autophagy. In brief, this system can remodel autophagy homeostasis and serve as an innovative approach for treatment of triple negative breast cancer.

中文翻译：

天然药物封装的 ROS 响应性纳米颗粒可重塑乳腺癌中的自噬稳态

在光动力疗法（PDT）中，活性氧（ROS）升高会激活肿瘤细胞保护性自噬，从而减弱治疗的抗肿瘤功能。因此，抑制肿瘤中的保护性自噬可以提高PDT的抗肿瘤效果。在此，制备了一种重塑自噬稳态的创新纳米中药系统（(TP+A)@TkPEG NPs）。光敏剂聚集诱导发射（AIE）和自噬调节剂雷公藤甲素（TP，雷公藤甲素的活性成分））被封装到ROS响应纳米颗粒中，以提高PDT治疗三阴性乳腺癌的抗肿瘤效果。我们证明，(TP+A)@TkPEG NPs 可以有效提高细胞内 ROS 水平，激活 TP 的 ROS 响应性释放，并在体外抑制 4T1 细胞的增殖。更重要的是，它大幅降低4T1细胞中自噬相关基因的转录和蛋白的表达，进而促进细胞凋亡。此外，该纳米草药治疗系统有效定向肿瘤位点，实现了肿瘤的高效抑制，并延长了4T1小鼠体内的生存时间。进一步的结果证实(TP+A)@TkPEG NPs显着抑制自噬相关起始基因( becline-1)的表达水平）和肿瘤微环境中的延伸蛋白（轻链3B），然后阻断PDT诱导的保护性自噬。简而言之，该系统可以重塑自噬稳态，并作为治疗三阴性乳腺癌的创新方法。

更新日期：2023-06-14

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