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The Convergence of Sonodynamic Therapy and Cuproptosis in the Dual-Responsive Biomimetic CytoNano for Precision Mitochondrial Intervention in Cancer Treatment.

Binyi LiZheng LiYing QianNan XiaoChunyun FanYong HuangAnwei ZhouXing-Hai Ning
Published in: Nano letters (2024)
The integration of sonodynamic therapy (SDT) with cuproptosis for targeted cancer treatment epitomizes a significant advancement in oncology. Herein, we present a dual-responsive therapeutic system, "CytoNano", which combines a cationic liposome infused with copper-nitride nanoparticles and oxygen-rich perfluorocarbon (Lip@Cu 3 N/PFC-O 2 ), all enveloped in a biomimetic coating of neutrophil membrane and acid-responsive carboxymethylcellulose. CytoNano leverages the cellular mimicry of neutrophils and acid-responsive materials, enabling precise targeting of tumors and their acidic microenvironment. This strategic design facilitates the targeted release of Lip@Cu 3 N/PFC-O 2 within the tumor, enhancing cancer cell uptake and mitochondrial localization. Consequently, it amplifies the therapeutic efficacy of both Cu 3 N-driven SDT and cuproptosis while preserving healthy tissues. Additionally, CytoNano's ultrasound responsiveness enhances intratumoral oxygenation, overcoming physiological barriers and initiating a combined sonodynamic-cuproptotic effect that induces multiple cell death pathways. Thus, we pioneer a biomimetic approach in precise sonodynamic cuproptosis, revolutionizing cancer therapy.
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