Affiliation:
1. Key Laboratory of Superlight Materials and Surface Technology Ministry of Education College of Materials Science and Chemical Engineering Harbin Engineering University Harbin 150001 P. R. China
2. College of Pharmacy Guangdong Medical University Dongguan 523808 People's Republic of China
3. School of Traditional Chinese Medicine Southern Medical University Guangzhou 510515 People's Republic of China
4. Department of Breast Surgery Second Affiliated Hospital of Harbin Medical University Harbin 150086 P. R. China
Abstract
AbstractFerroptosis, as a non‐apoptotic cell death pathway, has attracted increasing attention for cancer therapy. However, the clinical application of ferroptosis‐participated modalities is severely limited by the low efficiency owing to the intrinsic intracellular regulation pathways. Herein, chlorin e6 (Ce6) and N‐acetyl‐l‐cysteine‐conjugated bovine serum albumin‐ruthenium dioxide is elaborately designed and constructed for ultrasound‐triggered peroxynitrite‐mediated ferroptosis. Upon ultrasound stimulation, the sonosensitizers of Ce6 and RuO2 exhibit highly efficient singlet oxygen (1O2) generation capacity, which is sequentially amplified by superoxide dismutase and catalase‐mimicking activity of RuO2 with hypoxia relief. Meanwhile, the S‐nitrosothiol group in BCNR breaks off to release nitric oxide (NO) on‐demand, which then reacts with 1O2 forming highly cytotoxic peroxynitrite (ONOO−) spontaneously. Importantly, BCNR nanozyme with glutathione peroxidase‐mimicking activity can consume glutathione (GSH), along with the generated ONOO− downregulates glutathione reductase, avoiding GSH regeneration. The two‐parallel approach ensures complete depletion of GSH within the tumor, resulting in the boosted ferroptosis sensitization of cancer cells. Thus, this work presents a superior paradigm for designing peroxynitrite‐boosted ferroptosis sensitization cancer therapeutic.
Funder
National Natural Science Foundation of China
Natural Science Foundation of Shandong Province
Natural Science Foundation of Heilongjiang Province
China Postdoctoral Science Foundation
Heilongjiang Postdoctoral Science Foundation
Fundamental Research Funds for the Central Universities
Subject
Biomaterials,Biotechnology,General Materials Science,General Chemistry
Cited by
12 articles.
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