4.5 Article

Intraperitoneal administration of nanoparticles containing tocopheryl succinate prevents peritoneal dissemination

Journal

CANCER SCIENCE
Volume 113, Issue 5, Pages 1779-1788

Publisher

WILEY
DOI: 10.1111/cas.15321

Keywords

ascites; intraperitoneal administration; nanoparticles; peritoneal dissemination; tocopheryl succinate

Categories

Funding

  1. JSPS KAKENHI [18H03540]
  2. Grants-in-Aid for Scientific Research [18H03540] Funding Source: KAKEN

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Intraperitoneal administration of tocopheryl succinate nanoparticles can effectively prevent peritoneal dissemination of colon cancer and has anticancer effects. These nanoparticles can stably exist in the body and act by improving the intraperitoneal environment and inhibiting cancer cell proliferation.
Intraperitoneal administration of anticancer nanoparticles is a rational strategy for preventing peritoneal dissemination of colon cancer due to the prolonged retention of nanoparticles in the abdominal cavity. However, instability of nanoparticles in body fluids causes inefficient retention, reducing its anticancer effects. We have previously developed anticancer nanoparticles containing tocopheryl succinate, which showed high in vivo stability and multifunctional anticancer effects. In the present study, we have demonstrated that peritoneal dissemination derived from colon cancer was prevented by intraperitoneal administration of tocopheryl succinate nanoparticles. The biodistribution of tocopheryl succinate nanoparticles was evaluated using inductively coupled plasma mass spectroscopy and imaging analysis in mice administered quantum dot encapsulated tocopheryl succinate nanoparticles. Intraperitoneal administration of tocopheryl succinate nanoparticles showed longer retention in the abdominal cavity than by its intravenous (i.v.) administration. Moreover, due to effective biodistribution, tumor growth was prevented by intraperitoneal administration of tocopheryl succinate nanoparticles. Furthermore, the anticancer effect was attributed to the inhibition of cancer cell proliferation and improvement of the intraperitoneal microenvironment, such as decrease in the levels of vascular endothelial growth factor A, interleukin 10, and M2-like phenotype of tumor-associated macrophages. Collectively, intraperitoneal administration of tocopheryl succinate nanoparticles is expected to have multifaceted antitumor effects against colon cancer with peritoneal dissemination.

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