Spiky Magnetic Titania Particles for Integrated Exosome Capture and Metabolic Profiling Toward Cancer Diagnosis

Exosomal metabolite profiling represents a promising non-invasive approach for cancer diagnosis. However, its widespread application has been constrained by inefficient exosome isolation and cumbersome metabolomic workflows. Herein, we introduce a "magnetic-catcher" composite comprising a spiky TiO₂ shell with 3D nano-traps for efficient exosome capture via spatial complementarity and affinity interactions, and a superparamagnetic Fe₃O₄ core for rapid magnetic separation. Oxygen vacancies and heterointerfaces engineered on the shell enhance light absorption and charge separation, enabling the material to serve as an efficient matrix for laser desorption/ionization mass spectrometry (LDI-MS). During analysis, the particles simultaneously lyse captured exosomes and promote metabolite desorption/ionization, achieving high sensitivity and reproducibility (CV < 15%). Ultimately, an integrated magnetic-catcher/MALDI-MS platform was established, which consolidates exosome isolation and metabolomic analysis into a streamlined workflow. The integrated platform was applied to plasma from pancreatic ductal adenocarcinoma (PDAC) patients, yielding high-quality exosomal metabolic profiles. Machine learning analysis achieved accurate PDAC diagnosis and staging within the study cohort, with area under the curve (AUC) values of 1.000 for both tasks, and potential biomarkers (D-glucose, lysine, 6-methyloctanoic acid, phenyllactic acid, and 3-oxodecanoic acid) were identified. Future studies involving larger, multi‑center cohorts are required to validate the generalizability and clinical utility of our approach.