National Engineering Research Centre for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan, 430074, P. R. China.
Hubei Key Laboratory of Bioinorganic Chemistry and Materia Medical, Huazhong University of Science and Technology, Wuhan, 430074, P. R. China.
Angew Chem Int Ed Engl. 2022 Jul 4;61(27):e202203184. doi: 10.1002/anie.202203184. Epub 2022 May 5.
Imaging to evaluate tumor-associated neutrophils (TANs) is imperative for cancer immunotherapy but remains challenging. We herein report an activatable semiconducting polymer nanoprobe (SPCy) for near-infrared fluorescence (NIRF) and photoacoustic (PA) imaging of neutrophil elastase (NE), a biomarker of TANs. SPCy comprises a semiconducting polymer conjugated with a hemicyanine (hemi-Cy) dye caged by a NE-cleavable peptide as the side chain. After systemic administration, SPCy passively targets the tumor and reacts with NE to "uncage" the hemi-Cy, leading to enhanced NIRF and PA signals of the hemi-Cy but unchanged signals of the SP. Such NE-activated ratiometric NIRF and enhanced PA signals of SPCy correlate with the intratumoral population of TANs. Thus, this study not only presents the first TAN-specific PA probe, but also provides a general molecular design strategy for PA imaging of other immune-related biomarkers to facilitate screening of cancer immunotherapeutics.
用于评估肿瘤相关中性粒细胞 (TANs) 的成像对于癌症免疫疗法至关重要，但仍然具有挑战性。本文报道了一种用于中性粒细胞弹性蛋白酶 (NE) 的近红外荧光 (NIRF) 和光声 (PA) 成像的新型可激活半导体聚合物纳米探针 (SPCy)，NE 是 TANs 的生物标志物。SPCy 由与半花菁 (hemi-Cy) 染料共轭的半导体聚合物组成，该染料被 NE 可切割的肽作为侧链封闭。在系统给药后，SPCy 被动靶向肿瘤并与 NE 反应以“解笼”hemi-Cy，导致 hemi-Cy 的 NIRF 和 PA 信号增强，但 SP 的信号不变。SPCy 的这种 NE 激活的比率 NIRF 和增强的 PA 信号与肿瘤内 TANs 的群体相关。因此，本研究不仅提出了首个 TAN 特异性 PA 探针，而且还为其他免疫相关生物标志物的 PA 成像提供了通用的分子设计策略，以促进癌症免疫疗法的筛选。
