Urinary detection of therapy-induced senescence and fibrosis using an injectable albumin-based nanoprobe.

Abstract

Cellular senescence is a hallmark of age-related disorders, including cancer, in which senescence contributes to tumor progression and treatment resistance. Targeting senescent cells therapeutically requires noninvasive methods to longitudinally monitor senescence burden. Here, we present an injectable nanoprobe for noninvasive detection of therapy-induced senescence in lung cancer and pulmonary fibrosis via urine testing. Using human biopsy samples, clinical transcriptomic datasets and mouse models, we identify matrix metalloproteinase-7 (MMP-7) as a specific biomarker of senescence in lung cancer and bleomycin-induced fibrosis. 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 a nanoparticle growth-based assay, enabling longitudinal tracking of cisplatin-induced senescence and senolysis in mouse lung tumors and fibrosis. This approach offers a noninvasive and sensitive precision tool for monitoring senescence burden in lung cancer.