Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 21, 2018; 24(3): 351-359
Published online Jan 21, 2018. doi: 10.3748/wjg.v24.i3.351
Epidermal growth factor receptor-targeted immune magnetic liposomes capture circulating colorectal tumor cells efficiently
Jing-Hua Kuai, Qing Wang, Ai-Jun Zhang, Jing-Yu Zhang, Zheng-Feng Chen, Kang-Kang Wu, Xiao-Zhen Hu
Jing-Hua Kuai, Qing Wang, Ai-Jun Zhang, Jing-Yu Zhang, Zheng-Feng Chen, Kang-Kang Wu, Department of Gastroenterology, Qilu Hospital of Shandong University, Qingdao 266035, Shandong Province, China
Xiao-Zhen Hu, Department of General Surgery, Qilu Hospital of Shandong University, Qingdao 266035, Shandong Province, China
Author contributions: Kuai JH, Wang Q, Zhang AJ, Zhang JY, Chen ZF, Wu KK, and Hu XZ designed the research; Kuai JH, Wang Q, and Hu XZ performed the research; Zhang AJ and Zhang JY contributed new reagents/analytic tools; Kuai JH, Chen ZF, and Wu KK analyzed the data; and Kuai JH and Hu XZ wrote the paper.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of Qilu Hospital of Shandong University.
Conflict-of-interest statement: All the authors declare that there is no conflict of interest to disclose.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Xiao-Zhen Hu, PhD, Chief Doctor, Department of General Surgery, Qilu Hospital of Shandong University, No. 758, Hefei Road, Qingdao 266035, Shandong Province, China. hu.xz@qilu.edu.com
Telephone: +86-532-66850782 Fax: +86-532-66850532
Received: September 8, 2017
Peer-review started: September 8, 2017
First decision: September 20, 2017
Revised: November 27, 2017
Accepted: December 4, 2017
Article in press: December 4, 2017
Published online: January 21, 2018
ARTICLE HIGHLIGHTS
Research background

Metastasis contributes most to cancer-related deaths in patients with solid tumors. Mounting evidence suggests that circulating tumor cells (CTCs) which can shed from a primary tumor mass at the earliest stages of malignant progression, play a critical role in cancer metastasis. Detection and characterization of CTCs are challenging owing to their extreme scarcity in blood. However, the sensitivity of the aforementioned methods relies greatly on the degree of enrichment of CTCs and current techniques used are far from satisfactory. Recently, a new method, in which an epidermal growth factor receptor (EGFR) antibody-coupled magnetic liposome with a bilayer membrane structure was used, was developed. Studies showed that this method had a significant improvement in cell-capture efficiency owing to its enhanced interactions between the deformable antibody receptor-lipid bilayer structure and nanoscale cellular surface components. Such a high-affinity cell assay can be employed to recover cancer cells from spiked whole-blood samples in a stationary magnetic separation device.

Research motivation

The main topics are to compare the capacity of newly developed EGFR-targeted immune magnetic liposomes (EILs) vs epithelial cell adhesion molecule (EpCAM) immunomagnetic beads to capture colorectal circulating tumor cells (CTCs).

Research objectives

The main objectives were to compare the capacity of newly developed EILs vs EpCAM immunomagnetic beads to CTCs. And the significantly improved sensitivity of our new CTC capture technology might be useful in early detection of cancer metastasis and isolation of rare populations of cells.

Research methods

EILs were prepared using a two-step method, and the magnetic and surface characteristics were confirmed. The efficiency and specificity of EILs and EpCAM magnetic beads in capturing colorectal CTCs were compared. Statistical analyses were performed using Prism software (GraphPad Software, Inc., La Jolla, CA, United States). An unpaired Student’s t-test was used to compare hydrodynamic size, diffuse efficient, and zeta potential between IMLs and EILs. A paired Student’s t-test was used to detect differences in the number of CTCs captured by EpCAM immunomagnetic beads in comparison with EILs. A P-value < 0.05 was considered statistically significant.

Research results

The obtained EILs have a lipid nanoparticle structure similar to cell membrane. Improved binding with cancer cells was seen in EILs compared with the method of coupling nano/microspheres with antibody. The binding increased as the contact time extended. Compared with EpCAM immunomagnetic beads, EILs captured more CTCs in peripheral blood from colorectal cancer patients. The captured cells showed consistency with clinical diagnosis and pathology. Mutation analysis showed same results between captured CTCs and cancer tissues.

Research conclusions

Improved binding with cancer cells was seen in EILs compared with the method of coupling nano/microspheres with antibody. EILs were prepared using a two-step method and the magnetic and surface characteristics were confirmed. The efficiency and specificity in capturing colorectal CTCs were compared between EILs and EpCAM magnetic beads. EGFR-coated magnetic liposomes showed high efficiency and specificity in capturing colorectal CTCs. The captured cells showed consistency with clinical diagnosis and pathology. Mutation analysis showed same results between captured CTCs and cancer tissues. The significantly improved sensitivity of our new CTC capture technology might be useful in early detection of cancer metastasis and isolation of rare populations of cells.

Research perspectives

The significantly improved sensitivity of our new CTC capture technology might be useful in early detection of cancer metastasis and isolation of rare populations of cells.