Research Article: Uncovering the Binding Specificities of Lectins with Cells for Precision Colorectal Cancer Diagnosis Based on Multimodal Imaging

Date Published: April 19, 2018

Publisher: John Wiley and Sons Inc.

Author(s): Rongrong Tian, Hua Zhang, Hongda Chen, Guifeng Liu, Zhenxin Wang.


There is a high desire for novel targets/biomarkers to diagnose and treat colorectal cancer (CRC). Here, an approach starting from a polyacrylamide hydrogel–based lectin microarray is presented to screen the high expression of glycans on the CRC cell surface and to identify new lectin biomarkers for CRC. Three common CRC cell lines (SW480, SW620, and HCT116) and one normal colon cell line (NCM460) are profiled on the microarray with 27 lectins. The experimental results reveal that CRC cells highly express the glycans with d‐galactose, d‐glucose, and/or sialic acid residues, and Uelx Europaeus Agglutinin‐I (UEA‐I) exhibits reasonable specificity with SW480 cells. After conjugation of UEA‐I with silica‐coated NaGdF4:Yb3+, Er3+@NaGdF4 upconversion nanoparticles, the follow‐up in vitro and in vivo experiments provide further evidence on that UEA‐I can serve as tumor‐targeting molecule to diagnose SW480 tumor by multimodal imaging including upconversion luminescence imaging, T1‐weighted magnetic resonance imaging, and X‐ray computed tomography imaging.

Partial Text

Colorectal cancer (CRC) is one of the commonest alimentary system malignancy, which has relatively high incidence and mortality.1, 2, 3 Because of the commonality of malignancies including metastasis and recurrence, successful CRC therapy is strongly dependent on the detection of tumor at an earlier stage (early diagnosis), the correct identification of the subtype of cancer (precision treatment) and an accurate prediction of its likely course after suitable treatment (prognosis). For instance, the five year survival rate of patients with advanced CRC is significantly lower than that of patients with CRC at an early stage. Therefore, there is an urgent demand for novel biomarkers to diagnose CRC with high accuracy and sensitivity.

In summary, the present study provides a proof‐of‐principle demonstration of the screening candidate lectin biomarkers for CRC through direct profiling of binding affinities of living cells with lectins on PAAM hydrogel microarray. UEA‐I is identified to have specific binding affinity with SW480 cells by interactions of four kinds of colorectal organ/tumor–derived living cells with 27 lectins. After conjugation of UEA‐I with UCNP@SiO2—COOH, the UCNP@SiO2–UEA‐I provides high specificity toward mouse‐bearing SW480 tumor, and displays reasonable tumor contrasts as shown in multimodal imaging (UCL/MRI/CT) studies. This exemplifies its potential for noninvasive diagnosis of CRC at subtype level. Although only limited interactions of cells with lectins have been studied, the finding would open up possibilities for the future to discover lectins as biomarkers toward a broader biomedical application including cancer diagnosis and therapy.

Fabrication of the Polyacrylamide Hydrogel Microarray: The PAAM hydrogel microarray was prepared by the previously reported method with slight modifications.41 Using the SmartArray‐136 system (CapitalBio Ltd., China), the gel precursor aqueous solutions (3% w/v acrylamide, 0.12% w/v bis‐acrylamide, 10% w/v acrylic acid, and 15% v/v glycerol in water) were spotted on the benzophenone (BP)‐treated glass slides at the desired array by noncontact spraying, then each glass slide was covered with a quartz slide (125 mm × 40 mm × 1 mm) and irradiated by UV light (λ = 365 nm, light intensity = 4 mW cm−2) for 4 min. After photopolymerization, the slides were immersed in phosphate buffer (PB) solution (pH 5.7, 100 × 10−3m NaH2PO4·2H2O, and 15 × 10−3m Na2HPO4·12H2O) and shaken for 30 min at room temperature. After thoroughly washed by water (30 mL, 3 times), the PAAM hydrogel microarrays were activated by 1 mL of EDC and sulfo‐NHS solution (50 × 10−3m in 4‐morpholineethanesulfonic acid hydrate (MES) buffer, pH 5.7) for 1 h, followed by washing with 30 mL MES buffer (2 times) and 30 mL water (1 time), respectively. After dried by centrifugation (200 × g for 1 min), the activated PAAM hydrogel microarrays were stored at 4 °C.

The authors declare no conflict of interest.




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