Sialic acid-binding lectin-modified fructose-coated nanoparticles: a promising targeted therapeutic synthetic for breast cancers

Abstract

Background: Sialic acid-binding lectin (cSBL) specifically kills tumor cells rather than healthy cells. Glycopolymer-coated nanoparticles are selectively ingested by tumor cells because they can interact with the enriched carbohydrate receptors located on the surface of tumor cells. In this context, we synthesized cSBL-modified fructose-coated nanoparticles (LMFN) and cSBL-modified glucose-coated nanoparticles (LMGN) to investigate their anticancer activity in various molecular subtypes of breast cancer cell lines.Methods: The syntheses of fructose-coated nanoparticles and glucose-coated nanoparticles were based on the chemicals of 1,2:4,5-di-O-isopropylidene-β-d-fructopyranose and 1,2:4,5-di-O-isopropylidene-β-d-glucopyranose, respectively. The carbodiimide-based method was employed to synthesize LMFN and LMGN. The antitumor mechanism was explored by cell cycle analysis with flowcytometry and the antitumor activity was assessed by cytotoxicity assay and multiple drug effects analysis.Results: The cytotoxicity assay showed that LMFN had robust antitumor activity against all breast cancer phenotype cell lines whereas LMGN was rarely efficacious to against human epidermal growth factor receptor 2-positive/overexpression (HER2+/overexpression) breast cancer cells. The intrinsic reason for these findings was that the overexpression of fructose transporter, GLUT5, was observed in all breast cancer subtype cell lines but only a paucity of glucose transporter, GLUT1, was expressed in HER2+/overexpression breast cancer cell lines that dampened the uptake of LMGN to these cells. The cell cycle analysis indicated that the anticancer activity of LMFN was achieved by arresting cell cycle in S phase. The multiple drug effects analysis suggested the synergistic effect in the combinations of LMFN and tamoxifen to kill estrogen receptor+ breast cancer cells and LMFN and trastuzumab to kill HER2+/overexpressed breast cancer cells.Conclusion: Our work pinpoints that LMFN may be a new-onset selection for molecularly targeted therapy of breast cancers and paves the way for establishing its clinical application in the future.