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Uptake of intraperitoneally administrated triple helical β-glucan for antitumor in murine tumor models

Abstract

According to the principles of green chemistry and co-efficiency, natural polysaccharides with biological activities, especially immunoregulation and antitumor activities, have attracted much attention. However, lack of information concerning pharmacokinetics of polysaccharides becomes one of the major obstacles limiting their rational use in clinic. In this work, triple helical β-glucan (THG) isolated from Lentinus edodes, a β-1,6-branched β-1,3-glucan, was studied to clarify the cellular uptake after parenteral (e.g. intraperitoneal) administration and effect on immune cells in murine tumor models. The results of the size exclusion chromatography with static light scattering, differential refractometer and viscometer (SEC-LLS-RI-Vis) and atomic force microscopy (AFM) confirmed that three THG samples all displayed extended stiff chain conformation with apparent average contour lengths of 598 nm, 510 nm and 117 nm, respectively. The ex vivo results indicated that THG directly promoted cell proliferation of peritoneal macrophages, whole spleen cells and lymphocytes, and activated peritoneal macrophages with TNF-α production. In our findings, the intraperitoneally (i.p.) administrated THG was initially ingested by peritoneal resident macrophages, which transported it to lymph nodes, thymus and even tumor. Simultaneously, THG in macrophages was biodegraded into fragments with granular shapes and small size, which were active to be ingested easily by neutrophils. Furthermore, THG fragments could promote the infiltration of macrophages, neutrophils and DCs into tumors, as well as activate these cells to enhance their cytotoxicity to tumor cells, leading to apoptosis of tumor cells. This work provided important information concerning the ingestion and processing in vivo of triple helical β-glucan from natural products, leading to a better understanding of the antitumor mechanism through activating immune cells in murine tumor models.

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Publication details

The article was received on 04 Oct 2017, accepted on 07 Nov 2017 and first published on 08 Nov 2017


Article type: Paper
DOI: 10.1039/C7TB02649H
Citation: J. Mater. Chem. B, 2017, Accepted Manuscript
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    Uptake of intraperitoneally administrated triple helical β-glucan for antitumor in murine tumor models

    X. Zheng, Z. Fuling, X. Xu and L. Zhang, J. Mater. Chem. B, 2017, Accepted Manuscript , DOI: 10.1039/C7TB02649H

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