Nano-fuels-driven self-sacrificed ZIF-8@Apt integrated chip coupled with a DNAzyme system for the isolation and detection of glioblastoma-derived extracellular vesicles

Plasma extracellular vesicles (EVs) have emerged as promising biomarkers for the early diagnosis of glioblastoma. However, rapid and efficient isolation and detection of tumor-specific EV subsets from plasma remains challenging. To address this, we developed an innovative integrated chip based on self-sacrificial metal–organic frameworks and the epidermal growth factor receptor (EGFR) aptamers called ZIF-8@EGFR aptamer (ZIF-8@Apt), which further coupled with a “nano-fuels”-driven DNAzyme amplification strategy. The core functionality of the constructed chip lies in its ability to capture EVs with the ZIF-8@Apt module. Once captured, numerous DNA “nano-fuel” structures are in situ assembled on the EVs’ surfaces. Subsequently, the ZIF-8@Apt@EV@nano-fuels composites are lysed to release Zn 2+ , the EVs’ nucleic acids, and additional nano-fuels for subsequent detection. Finally, a DNAzyme detection system is introduced, where the released nano-fuels activate the DNAzyme, leading to multiple signal amplification aided by Zn 2+ for highly sensitive detection of plasma EVs. This integrated approach effectively enriches and detects target EVs, achieving a significantly enhanced detection sensitivity of 500 particles/μL. In a clinical study involving glioblastoma patients, our chip demonstrated a remarkable ability to distinguish between cancer patients and healthy individuals, achieving an area under the curve (AUC) of 0.958. Moreover, the response signals of the chip can be conveniently read using fluorescence spectroscopy or microscope, offering a rapid, highly sensitive, and high-throughput analysis of plasma EVs for various application scenarios. Overall, this study introduces a comprehensive approach for the rapid isolation and accurate analysis of plasma EVs, holding significant promise for early diagnosis and disease monitoring.