Cationic lipid-based nanoparticles mediate functional delivery of acetate to tumor cells in vivo leading to significant anticancer effects

Int J Nanomedicine. 2017 Sep 8:12:6677-6685. doi: 10.2147/IJN.S135968. eCollection 2017.

Abstract

Metabolic reengineering using nanoparticle delivery represents an innovative therapeutic approach to normalizing the deregulation of cellular metabolism underlying many diseases, including cancer. Here, we demonstrated a unique and novel application to the treatment of malignancy using a short-chain fatty acid (SCFA)-encapsulated lipid-based delivery system - liposome-encapsulated acetate nanoparticles for cancer applications (LITA-CAN). We assessed chronic in vivo administration of our nanoparticle in three separate murine models of colorectal cancer. We demonstrated a substantial reduction in tumor growth in the xenograft model of colorectal cancer cell lines HT-29, HCT-116 p53+/+ and HCT-116 p53-/-. Nanoparticle-induced reductions in histone deacetylase gene expression indicated a potential mechanism for these anti-proliferative effects. Together, these results indicated that LITA-CAN could be used as an effective direct or adjunct therapy to treat malignant transformation in vivo.

Keywords: cancer; epigenetics; lipid-based nanoparticles; liposomes; short-chain fatty acids.

MeSH terms

  • Acetates / administration & dosage*
  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Cations / chemistry
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / pathology
  • HCT116 Cells
  • HT29 Cells
  • Histone Deacetylases / genetics
  • Humans
  • Lipids / chemistry*
  • Liposomes / chemistry
  • Mice
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Xenograft Model Antitumor Assays

Substances

  • Acetates
  • Antineoplastic Agents
  • Cations
  • Lipids
  • Liposomes
  • Histone Deacetylases