Anti-Her2 affibody-decorated arsenene nanosheets induce ferroptosis through depleting intracellular GSH to overcome cisplatin resistance

• Published in: Journal of nanobiotechnology Vol. 21; no. 1; p. 203
• Main Authors: He, Peng, Xu, Shenglin, Miao, Zhaohua, Que, Yukang, Chen, Yu, Li, Sheng, Ma, Qiming, Yang, Rui, Wei, Wei, Zha, Zhengbao, Hu, Yong
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 27-06-2023; BioMed Central; BMC
• Subjects: Antimitotic agents; Antineoplastic agents; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Apoptosis; Arsenene nanosheets; Arsenic; B cells; Bone cancer; Bone Neoplasms - drug therapy; Cancer; Care and treatment; Cascade chemical reactions; Cell death; Cell Line, Tumor; Chemotherapy; Cisplatin; Cisplatin - pharmacology; Cisplatin - therapeutic use; Cisplatin resistance; Complications and side effects; Depletion; Diagnosis; Dosage and administration; Drug resistance; ErbB-2 protein; Ethanol; Ferroptosis; Flow cytometry; Glutathione; Glutathione - metabolism; Glutathione peroxidase; Health aspects; Humans; Intracellular; Leukemia; Lipid peroxidation; Lipids; Morphology; Nanomaterials; Nanosheets; Nanotechnology; Osteosarcoma; Osteosarcoma - drug therapy; Peroxidase; Peroxidation; Prevention; Proteins; Reactive oxygen species; Reactive Oxygen Species - metabolism; Sarcoma; Solid tumors; Synergistic effect; Tumor cells; Tumors; China; Arsenene nanosheets; Ferroptosis; Chemotherapy; Cisplatin resistance; Osteosarcoma
• ISSN: 1477-3155; 1477-3155
• DOI: 10.1186/s12951-023-01963-7

Ferroptosis, a form of regulated cell death induced by excessive accumulation of reactive oxygen species and lipid peroxidation, has recently attracted extensive attention due to its ability to effectively suppress tumors and overcome drug resistance. Unlike previously reported metal nanomaterials that induce ferroptosis via the Fenton reaction, arsenene nanosheets can effectively deplete intracellular glutathione and then induce ferroptosis by inhibiting glutathione peroxidase 4. In this study, we designed target-modified arsenene nanosheets loaded with cisplatin (Her2-ANs@CDDP), which are capable of selective uptake by tumor cells. Her2-ANs@CDDP promotes both apoptosis and ferroptosis through a reciprocal cascade reaction between cisplatin and the carrier, respectively, and we demonstrate that it can significantly inhibit the activity of drug-resistant cells. Arsenene nanosheets kill drug-resistant tumor cells by inducing ferroptosis and restoring the sensitivity of drug-resistant cells to cisplatin. Cisplatin-loaded arsenene nanosheets can be prepared simply, and exert synergistic effects that overcome drug resistance. They show great potential for applications in the clinical treatment of chemotherapy-insensitive osteosarcoma, expanding the uses of arsenic in the treatment of solid tumors.