An orthogonal barcoding enabled smart nanodevice for highly efficient isolation and proteomic profiling of...

Area of Science:

• Biochemistry
• Nanotechnology
• Oncology

Background:

• Tumor-derived extracellular vesicles (T-EVs) are crucial biomarkers due to their tumor-specific molecules.
• Protein cargo within T-EVs is vital for cancer progression, diagnosis, and therapy.
• T-EV heterogeneity presents challenges for effective biomarker utilization.

Purpose of the Study:

• To develop an orthogonal barcoding enabled smart nanodevice for T-EV isolation and proteomic profiling.
• To overcome challenges associated with T-EV heterogeneity and improve biomarker discovery.
• To validate the nanodevice's efficacy in identifying potential cancer biomarkers.

Main Methods:

• Developed a smart nanodevice using orthogonal labeling with aptamers against CD63 and EpCAM.
• Integrated T-EV isolation, protein extraction, and digestion within mesoporous silica foam (MOSF-tag) nanopores.
• Applied the nanodevice to serum samples from prostate cancer (PCa) patients for proteomic analysis.

Main Results:

• Successfully isolated T-EV subpopulations and performed in situ proteomic profiling.
• Achieved enhanced protein identification efficiency compared to traditional methods.
• Identified 832 proteins in PCa serum samples, with 113 significantly upregulated in PCa patients.

Conclusions:

• The smart nanodevice effectively isolates T-EVs and enables efficient proteomic profiling.
• Upregulated proteins in PCa patients show potential as biomarkers for early diagnosis and prognosis.
• This approach advances T-EV research and biomarker discovery for clinical applications.