新加坡南洋理工大学Kanyi Pu团队利用长距离单重态氧转移进行肿瘤内颗粒酶双酶锁定余辉成像。相关研究成果于2024年6月11日发表在《美国化学会杂志》。

利用两种生物标志物的正交效应，双锁定可激活光学探针在生物过程的特异性成像方面具有很大的前景。然而，他们的设计方法仅限于短距离能量或电荷转移机制，而信号读出依赖于荧光，这不可避免地会受到组织自发荧光的影响。

该文中，研究人员报道了一种长距离单线态氧转移方法，以开发一种双酶锁定的可激活余辉探针（BAAP），该探针在没有实时光激发的情况下发出持久的自发光，用于肿瘤内颗粒酶的动态成像。BAAP由免疫生物标记物激活的单线态氧（¹O₂）供体和癌症生物标记物活化的¹O₂受体组成，最初是非后发性的。

只有在存在免疫和癌症生物标志物的情况下，¹O₂才能由活化的供体产生，并随后向活化的受体扩散，从而产生明亮的近红外余辉，具有高的信号-背景比和对肿瘤内颗粒酶的特异性。因此，BAAP能实时跟踪肿瘤浸润的细胞毒性T淋巴细胞，从而能够以超高的灵敏度和特异性评估癌症免疫疗法，以及将肿瘤与局部炎症区分开来，这是单锁定探针无法实现的。

因此，该研究不仅提出了第一个双锁定余辉探针，还提出了一种通过活性氧转移过程实现双锁定探针的新设计方法。

附：英文原文

Title: Leveraging Long-Distance Singlet-Oxygen Transfer for Bienzyme-Locked Afterglow Imaging of Intratumoral Granule Enzymes

Author: Xin Wei, Cheng Xu, Penghui Cheng, Yuxuan Hu, Jing Liu, Mengke Xu, Jingsheng Huang, Yan Zhang, Kanyi Pu

Issue&Volume: June 11, 2024

Abstract: Dual-locked activatable optical probes, leveraging the orthogonal effects of two biomarkers, hold great promise for the specific imaging of biological processes. However, their design approaches are limited to a short-distance energy or charge transfer mechanism, while the signal readout relies on fluorescence, which inevitably suffers from tissue autofluorescence. Herein, we report a long-distance singlet oxygen transfer approach to develop a bienzyme-locked activatable afterglow probe (BAAP) that emits long-lasting self-luminescence without real-time light excitation for the dynamic imaging of an intratumoral granule enzyme. Composed of an immuno-biomarker-activatable singlet oxygen (1O2) donor and a cancer-biomarker-activatable 1O2 acceptor, BAAP is initially nonafterglow. Only in the presence of both immune and cancer biomarkers can 1O2 be generated by the activated donor and subsequently diffuse toward the activated acceptor, resulting in bright near-infrared afterglow with a high signal-to-background ratio and specificity toward an intratumoral granule enzyme. Thus, BAAP allows for real-time tracking of tumor-infiltrating cytotoxic T lymphocytes, enabling the evaluation of cancer immunotherapy and the differentiation of tumor from local inflammation with superb sensitivity and specificity, which are unachievable by single-locked probes. Thus, this study not only presents the first dual-locked afterglow probe but also proposes a new design way toward dual-locked probes via reactive oxygen species transfer processes.

DOI: 10.1021/jacs.4c05012

Source: https://pubs.acs.org/doi/abs/10.1021/jacs.4c05012