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Micromanipulation of Circulating Tumor Cells for Downstream Molecular Analysis and Metastatic Potential Assessment
Published on: May 14, 2019
Neutrophil membrane-coated immunomagnetic nanoparticles for efficient isolation and analysis of circulating tumor
Xianjia Wu1, Zhousheng Lin2, Chenchen Zhao1
1Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan, 430072, China; Institute of Biomedical Health Technology and Engineering, Shenzhen Bay Laboratory, Shenzhen, 518132, China.
Insights
Neutrophil membrane-coated immunomagnetic nanoparticles (IMNs) improve circulating tumor cell (CTC) isolation by reducing protein adsorption and white blood cell interference. This enhances CTC detection efficiency and viability for noninvasive cancer diagnosis.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cancer Diagnostics
Background:
- Circulating tumor cells (CTCs) are crucial biomarkers for noninvasive cancer diagnosis and precision medicine.
- Immunomagnetic nanoparticles (IMNs) are used for CTC isolation, but face challenges like non-specific protein adsorption (protein corona), white blood cell (WBC) interference, and reduced CTC viability.
- These limitations hinder the efficiency and accuracy of CTC isolation and analysis.
Purpose of the Study:
- To develop a novel surface functionalization strategy for IMNs to overcome existing limitations in CTC isolation.
- To enhance the efficiency, purity, and viability of isolated CTCs for improved cancer diagnosis.
Main Methods:
- Surface functionalization of IMNs with neutrophil cell membranes to create neutrophil membrane-coated IMNs (Neu-IMNs).
- Evaluation of Neu-IMNs in reducing non-specific protein adsorption and WBC interaction.
- Assessment of CTC separation efficiency, purity, and cell viability in spiked blood samples and patient blood samples.
- Confirmation of isolated CTCs' suitability for downstream cell sequencing.
Main Results:
- Neu-IMNs significantly reduced non-specific protein adsorption and WBC interference compared to bare IMNs.
- Neu-IMNs demonstrated superior CTC separation efficiency (41.36% to 96.82%) and purity (40.25% to 90.68%) in spiked blood samples.
- Successful isolation of CTCs from 19 out of 20 breast cancer patient blood samples using Neu-IMNs.
- Isolated CTCs were confirmed to be viable for downstream sequencing analysis.
Conclusions:
- Neutrophil membrane functionalization of IMNs is an effective strategy to enhance CTC isolation and analysis.
- Neu-IMNs offer improved performance by minimizing non-specific interactions and preserving cell viability.
- This approach provides a promising tool for early noninvasive cancer diagnosis and precision medicine through efficient CTC isolation and analysis.
Abstract:
The isolation and analysis of scarce circulating tumor cells (CTCs) with immunomagnetic nanoparticles (IMNs) have shown promising outcomes in noninvasive cancer diagnosis. However, the IMNs adsorb nonspecific proteins after entering into biofluids and the formed protein coronas cover surface targeting ligands, limiting the detection efficiency of IMNs. In addition, the interaction between surface targeting ligands and white blood cells (WBCs) significantly limits the purity of CTCs isolated by IMNs. Furthermore, the interfacial collision of nanoparticles and cells has negative effects on the viability of isolated CTCs. All of these limitations synthetically restrict the isolation and analysis of rare CTCs for early diagnosis and precision medicine. Here, we proposed that surface functionalization of IMNs with neutrophil membranes can simultaneously reduce nonspecific protein adsorption, enhance the interaction with CTCs, reduce the distraction from WBCs, and improve the viability of isolated CTCs. In spiked blood samples, our neutrophil membrane-coated IMNs (Neu-IMNs) exhibited a superior separation efficiency from 41.36% to 96.82% and an improved purity from 40.25% to 90.68% when compared to bare IMNs. Additionally, we successfully isolated CTCs in 19 out of total 20 blood samples from breast cancer patients using Neu-IMNs and further confirmed the feasibility of the isolated CTCs for downstream cell sequencing. Our work provides a new perspective on engineered IMNs for efficient isolation and analysis of CTCs, paving the way for early noninvasive diagnosis of cancer.
