Journal
CARBOHYDRATE POLYMERS
Volume 250, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.carbpol.2020.116904
Keywords
Polysaccharides; Lepidium meyenii Walp; Cationization; Tumor-associated macrophages; Immunotherapy
Categories
Funding
- National Natural Science Foundation of China [81760642]
- Key Natural Science Foundation of Yunnan Province, China [2018110506, 2017ZF004]
- Key project at central government of China [2060302]
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In the current study, we developed a synergistic chemo-immunotherapy using doxorubicin (Dox) and a natural polysaccharide as immunomodulator. First, we isolated a polysaccharide (MPW) from the root of Lepidium meyenii Walp. (maca) and characterized its chemical properties. MPW contains -> 4) -alpha-D-Glcp(1 -> glycosidic bonds, while the terminal alpha-D-Glcp(1 -> group is connected to the main chain through an O-6 bond. This polysaccharide was then modified by cationization (C-MPW) to enhance immunoregulatory activity. MPW and C-MPW were combined with Dox and their chemo-immunotherapy effects on 4T1 tumor-bearing mice were assessed. Results indicated that the combination of MPW/C-MPW exerted a stronger anti-tumor effect than Dox alone, while reducing systemic toxicity and inhibiting tumor metastasis. In addition, MPW and C-MPW exerted tumor immunotherapy effects through the NF-kappa B, STAT1, and STAT3 signaling pathways, redirecting TAMs to the M1 phenotype that facilitates immunological responses against tumors. As a result, the immunosuppressive tumor microenvironment was remodeled into an immune-activated state due to enhanced secretion of IL-12, TNF-alpha, and INF-gamma. Moreover, C-MPW exerted a stronger immunomodulatory effect than MPW. In conclusion, MPW and its cationic derivative are promising tools for cancer immunotherapy.
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