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

Li, Binyi; Li, Zheng; Qian, Ying; Xiao, Nan; Fan, Chunyun; Huang, Yong; Zhou, Anwei; Ning, Xinghai · Nano Lett · 2024

basic_science · Level V

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Abstract

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<sub>3</sub>N/PFC-O<sub>2</sub>), 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<sub>3</sub>N/PFC-O<sub>2</sub> within the tumor, enhancing cancer cell uptake and mitochondrial localization. Consequently, it amplifies the therapeutic efficacy of both Cu<sub>3</sub>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.

Medical subject headings