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Cancer immunotherapeutic effect of carboxymethylated β-d-glucan coupled with iron oxide nanoparticles via reprogramming tumor-associated macrophages.

Abstract
The cancer immunotherapeutic effect of a carboxymethylated β-d-glucan (CMPTR)/iron oxide nanoparticles (IONPs) system (CMPTR/IONPs) were investigated by using cell culture of bone marrow-derived macrophages (BMDMs) and B16F10 melanoma skin cancer-bearing mouse model. When compared with that of control group, CMPTR/IONPs-treated M2-like BMDMs exhibited upregulated M1 biomarkers expression, significantly inhibited the migration of B16F10 cancer cells (p < 0.05), and had the highest apoptotic percentage of B16F10 cancer cells (80.39 ± 8.73 %) in co-culture system. Intratumoral administration of CMPTR/IONPs significantly (p < 0.05) suppressed tumor growth (46.58 % based on tumor weight) in mice and enhanced the M1/M2 ratio from 0.40 ± 0.09 (control group) to 6.64 ± 1.61 in tumor associated macrophages (TAMs) which was higher than that of in CMPTR (1.27 ± 0.38), IONPs (1.38 ± 0.17). CMPTR/IONPs treatment also promoted apoptosis in cancer cells and increased the infiltration of CD4 and CD8 T-lymphocytes in tumor tissues. These results could be due to the combined effects of CMPTR and IONPs in the CMPTR/IONPs system, possibly mediated by the activation of NF-κB and IRF5 pathways for inducing M1 macrophages polarization and had potential cancer immunotherapeutic applications.
AuthorsYuting Su, Fan Yang, Mingfu Wang, Peter C K Cheung
JournalInternational journal of biological macromolecules (Int J Biol Macromol) Vol. 228 Pg. 692-705 (Feb 15 2023) ISSN: 1879-0003 [Electronic] Netherlands
PMID36566807 (Publication Type: Journal Article)
CopyrightCopyright © 2022. Published by Elsevier B.V.
Chemical References
  • Glucans
  • Irf5 protein, mouse
  • Interferon Regulatory Factors
Topics
  • Animals
  • Mice
  • Tumor-Associated Macrophages (pathology)
  • Glucans (therapeutic use)
  • Melanoma (drug therapy)
  • Immunotherapy
  • Magnetic Iron Oxide Nanoparticles
  • Nanoparticles
  • Interferon Regulatory Factors

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