Site-Specific Cascade-Activatable Fluorogenic Nanomicelles Enable Precision and Accuracy Imaging of Pulmonary Metastatic Tumor

• Published in: JACS Au Vol. 4; no. 7; pp. 2606 - 2616
• Main Authors: Chen, Xueqian, Liu, Jiatian, Zhang, Yong, Gao, Xueyun, Su, Dongdong
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 22.07.2024
• Subjects: lung metastasis; precise diagnosis; cascade activation; Imaging; NIR fluorogenic nanomicelles
• ISSN: 2691-3704; 2691-3704
• DOI: 10.1021/jacsau.4c00356

The precise localization of metastatic tumors with subtle growth is crucial for timely intervention and improvement of tumor prognosis but remains a paramount challenging. To date, site-specific activation of fluorogenic probes for single-stimulus-based diagnosis typically targets an occult molecular event in a complex biosystem with limited specificity. Herein, we propose a highly specific site-specific cascade-activated strategy to enhance detection accuracy, aiming to achieve the accurate detection of breast cancer (BC) lung metastasis in a cascade manner. Specifically, cascade-activatable NIR fluorogenic nanomicelles HPNs were constructed using ultra-pH-sensitive (UPS) block copolymers as carriers and nitroreductase (NTR)-activated fluorogenic reporters. HPNs exhibit programmable cascade response characteristics by first instantaneous dissociating under in situ tumor acidity, facilitating deep tumor penetration followed by selective fluorescence activation through NTR-mediated enzymatic reaction resulting in high fluorescence ON/OFF contrast. Notably, this unique feature of HPNs enables high-precision diagnosis of orthotopic BC as well as its lung metastases with a remarkable signal-to-background ratio (SBR). This proposed site-specific cascade activation strategy will offer opportunities for a specific diagnosis with high signal fidelity of various insidious metastatic lesions in situ across different diseases.