Wei Rao, Lei Ling, Wu Ling-Ling, Zhang Leilei, Hu Hai-Yu
Pharmacy department Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100020, China.
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China.
Chembiochem. 2025 Mar 15;26(6):e202400990. doi: 10.1002/cbic.202400990. Epub 2025 Jan 29.
Bacterial infections, particularly those caused by drug-resistant bacteria, represent a pressing global health challenge. During the interaction between pathogen infection and host defense, bacterial infections initiate the host's immune response, which involves the activation of proteases that play a critical role in antibacterial defense. Granzyme B (GzmB), a key immune-related biomarker associated with cytotoxic T lymphocytes (CTLs), plays a pivotal role in this process. Therefore, detecting the activity of GzmB is crucial for understanding the host immune response to bacterial infections and for developing therapeutic strategies to overcome bacterial virulence. In this study, we designed and synthesized three granzyme B-activated near-infrared molecular probes. Among them, the probe HCy-F demonstrates in situ imaging capability, enabling precise quantification of GzmB activity. This development offers a valuable tool for monitoring immune responses and optimizing immunotherapy approaches for combating drug-resistant pathogens.
细菌感染，尤其是由耐药细菌引起的感染，是全球紧迫的健康挑战。在病原体感染与宿主防御的相互作用过程中，细菌感染引发宿主的免疫反应，这涉及到蛋白酶的激活，而这些蛋白酶在抗菌防御中起关键作用。颗粒酶B（GzmB）是一种与细胞毒性T淋巴细胞（CTL）相关的关键免疫相关生物标志物，在这一过程中起关键作用。因此，检测GzmB的活性对于理解宿主对细菌感染的免疫反应以及制定克服细菌毒力的治疗策略至关重要。在本研究中，我们设计并合成了三种颗粒酶B激活的近红外分子探针。其中，探针HCy-F具有原位成像能力，能够精确量化GzmB活性。这一进展为监测免疫反应和优化对抗耐药病原体的免疫治疗方法提供了有价值的工具。
