Hierarchical Flower-Like UiO-66@TiO₂ Heterostructure for On-Plate Exosome Enrichment and In Situ Metabolic...

The efficient capture and sensitive detection of exosomes from complex biological samples remain critical challenges for liquid biopsy-based cancer diagnosis. Herein, we report a three-dimensional flower-like UiO-66@TiO₂ heterostructure that integrates on-plate exosome enrichment with in situ laser desorption/ionization mass spectrometry (LDI-MS) analysis. The hierarchical flower-like architecture (approximately 2 µm) provides a high surface area and abundant binding sites for exosome capture, while the Type II heterojunction between UiO-66 and TiO₂ facilitates photogenerated charge separation, significantly enhancing photothermal conversion, charge transfer, and molecular desorption upon laser irradiation. The established platform achieves a detection limit of 2.3 × 10⁵ particles per mL for exosomes with excellent reproducibility and anti-interference capability. When applied to a clinical cohort of 678 serum samples from patients with prostate cancer (PCa), benign prostatic disease (BPD), and healthy controls (HC), the platform enables rapid acquisition of exosome metabolic and lipid fingerprints. Machine learning analysis of these fingerprints successfully distinguishes prostate disease (PD) from HC and PCa from BPD. In an external validation cohort, the model identified 97.1% of HC, 86.4% of BPD, and 91.3% of PCa cases. This work provides a promising strategy for exosome-based liquid biopsy and highlights the potential of functional nanomaterials in precision oncology.