Collagens are fibrous proteins that are integral to the strength and stability of connective tissues. During collagen maturation, lysyl oxidases (LOX) initiate the cross-linking of fibers, but abnormal LOX activity is associated with impaired tissue function as seen in fibrotic and malignant diseases. Visualizing and targeting this dynamic process in healthy and diseased tissue is important, but so far not feasible. Here we present a probe for the simultaneous monitoring and targeting of LOX-mediated collagen cross-linking that combines a LOX-activity sensor with a collagen peptide to chemoselectively target endogenous aldehydes generated by LOX. This synergistic probe becomes covalently anchored and lights up in vivo and in situ in response to LOX at the sites where cross-linking occurs, as demonstrated by staining of normal skin and cancer sections. We anticipate that our reactive collagen-based sensor will improve understanding of collagen remodeling and provide opportunities for the diagnosis of fibrotic and malignant diseases.

胶原蛋白是纤维蛋白，对结缔组织的强度和稳定性不可或缺。在胶原成熟过程中，赖氨酰氧化酶 (LOX) 启动纤维的交联，但异常的 LOX 活性与纤维化和恶性疾病中所见的组织功能受损有关。在健康和患病组织中可视化和定位这种动态过程很重要，但到目前为止还不可行。在这里，我们提出了一种同时监测和靶向 LOX 介导的胶原交联的探针，该探针将 LOX 活性传感器与胶原肽相结合，以化学选择性地靶向 LOX 产生的内源性醛。这种协同探针在发生交联的位点响应 LOX，在体内和原位变成共价锚定并点亮，正如正常皮肤和癌症切片的染色所证明的那样。我们预计，我们的反应性胶原蛋白传感器将提高对胶原蛋白重塑的理解，并为纤维化和恶性疾病的诊断提供机会。