Department of NanoEngineering, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA.
Herman Ostrow School of Dentistry, University of Southern California, 925 West 34th Street, Los Angeles, CA 90089, USA.
Angew Chem Int Ed Engl. 2022 Jul 25;61(30):e202201843. doi: 10.1002/anie.202201843. Epub 2022 Jun 13.
Porphyromonas gingivalis is a keystone pathogen in periodontal disease. We herein report a dual-modal fluorescent and photoacoustic imaging probe for the detection of gingipain proteases secreted by P. gingivalis. Upon proteolytic cleavage by Arg-specific gingipain (RgpB), five-fold photoacoustic enhancement and >100-fold fluorescence activation was measured with detection limits of 1.1 nM RgpB and 5.0E4 CFU mL bacteria in vitro. RgpB activity was imaged in porcine jaws with low-nanomolar sensitivity. Diagnostic efficacy was evaluated in gingival crevicular fluid samples from subjects with and without periodontal disease, wherein activation was correlated to qPCR-based detection of P. gingivalis (Pearson's r=0.71). Finally, photoacoustic imaging of RgpB-cleaved probe was achieved in murine brains ex vivo, with relevance and potential utility for disease models of general infection by P. gingivalis, motivated by the recent biological link between gingipain and Alzheimer's disease.
牙龈卟啉单胞菌是牙周病的关键病原体。我们在此报告了一种双模式荧光和光声成像探针，用于检测牙龈卟啉单胞菌分泌的牙龈蛋白酶。经精氨酸特异性牙龈蛋白酶（RgpB）酶切后，在体外检测限为 1.1 nM RgpB 和 5.0E4 CFU/mL 细菌时，可测量到五倍的光声增强和 >100 倍的荧光激活。RgpB 活性在猪颌骨中以低纳摩尔灵敏度进行成像。在患有和不患有牙周病的受试者的牙龈沟液样本中评估了诊断功效，其中激活与基于 qPCR 的牙龈卟啉单胞菌检测呈正相关（Pearson r=0.71）。最后，在离体小鼠脑中实现了 RgpB 切割探针的光声成像，这与牙龈蛋白酶与阿尔茨海默病之间的最近生物学联系有关，为一般感染性疾病模型提供了相关性和潜在的应用价值。
