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Arginine-Rich Manganese Silicate Nanobubbles as a Ferroptosis-Inducing Agent for Tumor-Targeted Theranostics

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journal contribution
posted on 29.11.2018, 00:00 by Shuaifei Wang, Fangyuan Li, Ruirui Qiao, Xi Hu, Hongwei Liao, Lumin Chen, Jiahe Wu, Haibin Wu, Meng Zhao, Jianan Liu, Rui Chen, Xibo Ma, Dokyoon Kim, Jihong Sun, Thomas P. Davis, Chunying Chen, Jie Tian, Taeghwan Hyeon, Daishun Ling
Ferroptosis, an iron-based cell-death pathway, has recently attracted great attention owing to its effectiveness in killing cancer cells. Previous investigations focused on the development of iron-based nanomaterials to induce ferroptosis in cancer cells by the up-regulation of reactive oxygen species (ROS) generated by the well-known Fenton reaction. Herein, we report a ferroptosis-inducing agent based on arginine-rich manganese silicate nanobubbles (AMSNs) that possess highly efficient glutathione (GSH) depletion ability and thereby induce ferroptosis by the inactivation of glutathione-dependent peroxidases 4 (GPX4). The AMSNs were synthesized via a one-pot reaction with arginine (Arg) as the surface ligand for tumor homing. Subsequently, a significant tumor suppression effect can be achieved by GSH depletion-induced ferroptosis. Moreover, the degradation of AMSNs during the GSH depletion contributed to T1-weighted magnetic resonance imaging (MRI) enhancement as well as on-demand chemotherapeutic drug release for synergistic cancer therapy. We anticipate that the GSH-depletion-induced ferroptosis strategy by using manganese-based nanomaterials would provide insights in designing nanomedicines for tumor-targeted theranostics.