Urinary Detection of Therapy-induced Senescence and Fibrosis Using an Injectable Albumin-based Nanoprobe

Cellular senescence is a hallmark of cancer and age-related disorders. In cancer, senescence can arise from oncogenic activation or therapy-induced genotoxic stress, contributing to tumor progression and treatment resistance. Growing interest in senescence-targeting therapeutics (senotherapies) highlights the need for non-invasive methods for longitudinal monitoring of senescence. Here, we present an injectable nanoprobe for non-invasive detection of therapy-induced senescence (TIS) in lung cancer and pulmonary fibrosis via urine testing. Using human biopsy samples, murine models, and transcriptomic datasets, we identify matrix metalloproteinase-7 (MMP-7) as a specific biomarker of chemotherapy-induced senescence in lung cancer. Based on this, we develop ALBANC, a nanoprobe composed of human serum albumin linked to gold nanoclusters (AuNCs) through MMP-7-cleavable peptide linkers. MMP-7-mediated cleavage releases AuNCs that are renally excreted, enabling rapid and sensitive colorimetric urine detection via nanoparticle growth-based assay. This platform enables longitudinal tracking of cisplatin-induced senescence and senolytic responses in mouse lung tumors, as well as early detection of pulmonary fibrosis in bleomycin-induced models, a pathology associated with elevated MMP-7 levels. Together, this approach offers a non-invasive and sensitive strategy for monitoring TIS in lung cancer and potentially other senescence-related diseases with poor prognosis, such as fibrosis