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Orthogonal Coding-Guided Liposomal Nanoreactor for One-Pot Precise Proteomic Profiling of Tumor-Derived Extracellular
Qian Shi1, Xuedong Huang1, Bin Li1
1Department of Chemistry, Shanghai Stomatological Hospital, School of Pharmacy, Institute of Biomedical Sciences, Fudan University, Shanghai 200438, China.
Nano Letters
|August 11, 2025
Summary
We developed a novel nanoreactor (OLEN) for rapid proteomic profiling of tumor-derived extracellular vesicles (TEVs) from liquid biopsies. This technology enhances cancer diagnosis by identifying key protein biomarkers in prostate cancer patients.
Area of Science:
- Biochemistry
- Nanotechnology
- Molecular Diagnostics
Background:
- Tumor-derived extracellular vesicles (TEVs) contain protein biomarkers for cancer diagnosis.
- EV heterogeneity and complex assays limit the clinical application of TEVs.
- Current methods require large sample volumes and extensive processing.
Purpose of the Study:
- To develop a streamlined, one-pot method for proteomic profiling of TEVs.
- To enhance the sensitivity and specificity of EV biomarker detection.
- To create a platform for noninvasive cancer diagnostics using liquid biopsies.
Main Methods:
- Developed an orthogonal coding-guided liposomal enzyme nanoreactor (OLEN).
- Integrated DNA computation for selective recognition of CD63+EpCAM+ TEVs.
- Utilized targeted membrane fusion for in situ protein extraction and digestion within EVs.
Main Results:
- OLEN achieved one-pot proteomic profiling of TEVs from 10 μL of plasma.
- Identified 525 proteins, covering over 86.5% of EV proteins, with 81.7% tumor-associated.
- Detected over 200 differentially expressed proteins between prostate cancer (PCa) and benign prostatic hyperplasia (BPH).
Conclusions:
- OLEN offers a modular, streamlined workflow for EV-based liquid biopsy.
- The platform demonstrates potential for sensitive and noninvasive cancer diagnostics.
- Identified potential PCa progression biomarkers through differential proteomic analysis.
