4.7 Article

Preparation and characterization of folic acid conjugated sulfated polysaccharides on NK cell activation and cellular uptake in HeLa cells

Journal

CARBOHYDRATE POLYMERS
Volume 254, Issue -, Pages -

Publisher

ELSEVIER SCI LTD
DOI: 10.1016/j.carbpol.2020.117250

Keywords

Codium fragile; Folic acid; Conjugation; Folate receptor; NK cells; HeLa cells

Funding

  1. Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education [2018R1A6A1A03023584]

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In this study, the sulfated polysaccharide (SP) of Codium fragile was conjugated to folic acid (SP-FA) through esterification reaction, showing no direct toxicity on NK cells and HeLa cells. Treatment with SP and SP-FA enhanced NK cells cytotoxicity against HeLa cells by upregulating IFN-gamma, TNF-alpha, perforin, and Granzyme-B, while also activating NK cells through NF-KB and MAPK pathways. The binding capacity studies demonstrated the targeting ability of SP-FA towards FR-overexpressed cancer cells, suggesting its potential as a selective drug delivery system.
In this study, the sulfated polysaccharide (SP) of Codium fragile was conjugated to folic acid (SP-FA). FT-IR and H-1 NMR techniques revealed the occurrence of esterification reaction between the hydroxyl group of SP and the gamma-carboxyl group of FA that confirming the SP-FA conjugation. SP and SP-FA did not show any direct toxicity on NK cells and HeLa cells. However, the treatment of SP and SP-FA enhance the NK cells cytotoxicity against HeLa cells by the upregulation of IFN-gamma, TNF-alpha, perforin, and Granzyme-B. Moreover, NK cells activation was stimulated through NF-KB and MAPK pathways. The binding capacity studies exposed the targeting ability of HeLa cells by folate receptor (FR) which was assessed by a confocal quantitative image cytometer analysis. These results indicate that SP-FA could be used as selective drug delivery systems for targeting FR-overexpressed cancer cells with less toxicity.

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