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Novel Peptide-Based Magnetic Nanoparticle for Mesenchymal Circulating Tumor Cells Detection
Fei Jia1,2, Yuehua Wang1,2, Zhiguo Fang1,2
1CAS Key Laboratory of Standardization and Measurement for Nanotechnology, CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology, Beijing 100190, China.
This study introduces a new method for isolating mesenchymal circulating tumor cells (CTCs) using N-cadherin targeting magnetic nanoparticles (NP@MNPs). This complements existing EpCAM methods, enabling comprehensive CTC analysis for better cancer prognosis and treatment evaluation.
Area of Science:
- Oncology
- Biotechnology
- Nanotechnology
Background:
- Circulating tumor cells (CTCs) monitoring is crucial for cancer prognosis and treatment evaluation.
- Existing EpCAM-based CTC enrichment platforms miss mesenchymal CTCs due to epithelial-mesenchymal transition (EMT).
- N-cadherin is overexpressed on mesenchymal CTCs and promotes cancer cell migration.
Purpose of the Study:
- To develop a novel CTCs isolation approach targeting N-cadherin to capture mesenchymal CTCs.
- To complement existing EpCAM-based methods for comprehensive CTC analysis.
- To lay the foundation for mesenchymal CTC isolation and subsequent molecular analysis.
Main Methods:
- Screening of a novel peptide (NP) targeting N-cadherin.
- Development of NP-functionalized magnetic nanoparticles (NP@MNPs) for CTC isolation.
- Spiking human blood with CTCs for capture efficiency assessment.
- Single-cell level RNA sequencing of captured CTCs.
Main Results:
- NP@MNPs demonstrated high capture efficiency (approx. 85%) for mesenchymal CTCs.
- Combined use of NP@MNPs and EP@MNPs allowed for distinguishing epithelial and mesenchymal CTC subgroups.
- RNA profiles confirmed the distinction between epithelial and mesenchymal CTCs.
Conclusions:
- A novel CTCs isolation platform using NP@MNPs effectively captures mesenchymal CTCs.
- This approach addresses the limitations of EpCAM-based methods for heterogeneous CTC populations.
- The developed platform enables comprehensive molecular analysis of both epithelial and mesenchymal CTCs, advancing cancer diagnostics.
