Visualizing Efficacy of Antineoplastic Drug via Ratiometric Near-Infrared Fluorescence Imaging of Tumor-Associated Macrophage-Specific Nitric Oxide
Chuanchen Wu, Fanghui Zhang, Yuantao Mao, Xinru Qi, Xin Wang, Wen Zhang, Bo Tang, Ping Li
Abstract
High Resolution Image Download MS PowerPoint Slide Elevated nitric oxide (NO) within tumor-associated macrophages (TAMs) suggests a reduction of TAM-mediated tumoral immune tolerance. This cellular event could be a reliable indicator for efficacy evaluation of antineoplastic drugs. However, a suitable method for TAM-specific NO measurement is still lacking. In this work, a simple and fast efficacy evaluation method for antineoplastic drugs is established based on a ratiometric TAM-specific NO near-infrared (NIR) fluorescence probe TAM-Cy-NO. Molecular fluorescence probe Cy-NO for NO response was encapsulated in the TAM-targeting peptide (M2pep)-functionalized liposome to construct TAM-Cy-NO. After TAM enters through M2pep, Cy-NO reacts with NO specifically, resulting in a dose-dependent ratiometric fluorescence signal ( I 610 / I 815 ) change manner. Utilizing this strategy, we observed that PLX-3397, metformin, and ibrutinib triggered NO generation within TAM greater than that with sorafenib. Notably, metformin and ibrutinib promoted TNF-α and reduced PD-L1 expressions, which suggest reductions of TAM-mediated immunosuppression. As expected, these drugs delayed tumor progression in mice. This method provides a promising efficacy evaluation strategy for rapid screening of antineoplastic drugs.