Evolving an Ultra-Sensitive Near-Infrared β-Galactosidase Fluorescent Probe for Breast Cancer Imaging and Surgical Resection Navigation.
|
| Abstract |
Early diagnosis and therapy are clinically crucial in decreasing mortality from breast carcinoma. However, the existing probes have difficulty in accurately identifying the margins and contours of breast carcinoma due to poor sensitivity and specificity. There is an urgent need to develop high-sensitive fluorescent probes for the diagnosis of breast carcinoma and for differentiating tumors from normal tissues during surgery. β-Galactosidase is a significant biomarker, whose overexpression is closely associated with the progression of breast tumors. Herein, we have constructed a β-galactosidase-activated fluorescent probe NIR-βgal-2 through rational design and molecular docking engineering simulations. The probe displayed superior sensitivity (detection limit = 2.0 × 10-3 U/mL), great affinity (Km = 1.84 μM), and catalytic efficiency (kcat/Km = 0.24 μM-1 s-1) for β-galactosidase. Leveraging this probe, we demonstrated the differentiation of cancer cells overexpressing β-galactosidase from normal cells and then applied the probe for intraoperative guided excision of breast tumors. Moreover, we exhibited the application of NIR-βgal-2 for the successful resection of orthotopic breast tumors by "in situ spraying" and monitored a good prognostic recovery. This work may promote the application of enzyme-activated near-infrared fluorescent probes for the development of carcinoma diagnosis and image-guided surgery.
|
|---|---|
| Authors | Qian Wu, Qian-Hui Zhou, Wei Li, Tian-Bing Ren, Xiao-Bing Zhang, Lin Yuan |
| Journal | ACS sensors (ACS Sens) Vol. 7 Issue 12 Pg. 3829-3837 (12 23 2022) ISSN: 2379-3694 [Electronic] United States |
| PMID | 36383027 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
| Chemical References |
|
| Topics |
|
Join CureHunter, for free Research Interface BASIC access!
Realize the full power of the drug-disease research graph!