Effective cancer immunotherapy by Ganoderma lucidum polysaccharide-gold nanocomposites through dendritic cell activation and memory T cell response

Carbohydr Polym. 2019 Feb 1;205:192-202. doi: 10.1016/j.carbpol.2018.10.028. Epub 2018 Oct 13.

Abstract

Polysaccharides purified from natural herbs possess immunoregulatory functions, while the efficacy of natural polysaccharides on cancer treatment remains unreliable, likely due to their low prescribed doses and fast clearances in clinical settings. In this study, gold nanocomposites containing Ganoderma lucidum polysaccharide (GLP-Au) efficiently induced dendritic cell (DC) activation, evident by the increase of CD80/CD86/CD40/MHCII, decrease of phagocytic ability and acid phosphatase activity, and increased cytokine transcription. GLP-Au significantly promoted the proliferation of CD4+ and CD8+ T cells in splenocytes. DC/T cell co-culture study proved that GLP-Au activation on DC directly resulted in T cell proliferation. GLP-Au exhibited strong inhibitory effects on 4T1 tumor growth and pulmonary metastasis when combined with doxorubicin. GLP-Au recovered body weight loss by doxorubicin and increased the percentage of CD4+/CD44+ memory T cells. This work suggests that polysaccharides from natural herbs can be incorporated into nanocomposites with immunoregulatory characteristics for enhanced efficacy on tumor therapy.

Keywords: Cancer therapy; Dendritic cell; Immunoregulation; Nanoparticle; Polysaccharides.

MeSH terms

  • Adjuvants, Immunologic / chemical synthesis
  • Adjuvants, Immunologic / pharmacology
  • Adjuvants, Immunologic / therapeutic use*
  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Breast Neoplasms / therapy*
  • CD4-Positive T-Lymphocytes / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dendritic Cells / drug effects
  • Doxorubicin / therapeutic use
  • Drug Combinations
  • Gold / chemistry
  • Immunotherapy / methods*
  • Mice
  • Nanocomposites / chemistry*
  • Neoplasm Metastasis / prevention & control
  • Polysaccharides / chemistry
  • Polysaccharides / pharmacology
  • Polysaccharides / therapeutic use*
  • Reishi / chemistry
  • Tissue Distribution

Substances

  • Adjuvants, Immunologic
  • Antineoplastic Agents
  • Drug Combinations
  • Polysaccharides
  • Gold
  • Doxorubicin