Lung adenocarcinoma (LUAD) is a disease of unmet need due to its high lethality. Platinum-based chemotherapy is commonly used for first line management, often in combination with immunotherapy, but treatment resistance continues to be one of the major challenges to overcome. Recently, we reported that platinum therapy induces a senescent response in cancer cells and the tumour microenvironment featured by a TGFBeta secretome (SASP) that strongly promotes tumour progression and relapse by activating the AKT/mTOR pathway (Gonzalez-Gualda et al., Nature Aging 2026). Targeting this platinum tumour-promoting senescent secretome in combination with senolytics (navitoclax) or senomorphics (TGFBRI inhibitors) significantly reduces the tumour burden and increases survival in mice. However, longitudinal monitoring of senescence in vivo remains a major challenge.

This study employs sophisticated techniques for nanomaterials synthesis, functionalization and validation; murine models of lung cancer; and clinical samples, datasets and scRNAseq analyses from LUAD patients at NHS Royal Papworth Hospital.

We report an injectable nanoprobe enabling non-invasive detection of therapy-induced senescence (TIS) in lung cancer through urine-based analysis. Integrating patient-derived samples, murine models, and transcriptomic datasets, we identify matrix metalloproteinase-7 (MMP-7) as a selective biomarker of chemotherapy-induced senescence in lung cancer. Leveraging this insight, we developed ALBANC, a protease-responsive nanoprobe comprising human serum albumin conjugated to gold nanoclusters (AuNCs) via MMP-7–cleavable peptide linkers. MMP-7–mediated cleavage releases AuNCs for renal excretion, enabling rapid and highly sensitive colorimetric detection in urine. To further amplify detection sensitivity, we implemented a nanoparticle alloy formation (growth–based) assay that enhances urinary AuNC signal by ~250-fold relative to conventional peroxidase-mimicking methods. This platform enabled longitudinal tracking of cisplatin-induced senescence in murine lung tumors and quantitative assessment of senolytic responses. At the translational level, ALBANC nanoprobe may potentially be applied for longitudinal monitoring of lung cancer patients response to chemotherapy, as a prognostic biomarker for therapy resistance and, ultimately, for the evaluation of the senescent burden upon senotherapeutic treatment.

Together, ALBANC nanoprobe offers a non-invasive strategy for monitoring therapy-induced senescence in lung cancer and may be broadly applicable to other senescence-related conditions, providing preclinical proof-of-concept for future trial designs. Hartono M et al., (Munoz-Espin D*). Nature Aging. In Press.

D.M.-E. was supported by a CRUK Program Foundation Award (C62187/A29760) and a CRUK Early Detection Project Award (C62187/A26989).