Rationalizing the use of functionalized poly-lactic-co-glycolic acid nanoparticles for dendritic cell-based targeted anticancer therapy

Nanomedicine (Lond). 2016;11(5):479-94. doi: 10.2217/nnm.15.213. Epub 2016 Feb 19.

Abstract

Background: Delivery of PLGA (poly [D, L-lactide-co-glycolide])-based biodegradable nanoparticles (NPs) to antigen presenting cells, particularly dendritic cells, has potential for cancer immunotherapy.

Materials & methods: Using a PLGA NP vaccine construct CpG-NP-Tag (CpG-ODN-coated tumor antigen [Tag] encapsulating NP) prepared using solvent evaporation technique we tested the efficacy of ex vivo and in vivo use of this construct as a feasible platform for immune-based therapy.

Results: CpG-NP-Tag NPs were avidly endocytosed and localized in the endosomal compartment of bone marrow-derived dendritic cells. Bone marrow-derived dendritic cells exposed to CpG-NP-Tag NPs exhibited an increased maturation (higher CD80/86 expression) and activation status (enhanced IL-12 secretion levels). In vivo results demonstrated attenuation of tumor growth and angiogenesis as well as induction of potent cytotoxic T-lymphocyte responses.

Conclusion: Collectively, results validate dendritic cells stimulatory response to CpG-NP-Tag NPs (ex vivo) and CpG-NP-Tag NPs' tumor inhibitory potential (in vivo) for therapeutic applications, respectively.

Keywords: DCs; NP; breast cancer; cancer vaccines; dendritic cells; immunotherapy; nanoparticle.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cancer Vaccines / administration & dosage*
  • Cancer Vaccines / chemistry
  • Cancer Vaccines / immunology
  • Dendritic Cells / drug effects*
  • Dendritic Cells / immunology
  • Endocytosis / immunology
  • Humans
  • Immunotherapy / methods
  • Lactic Acid / administration & dosage
  • Lactic Acid / chemistry
  • Molecular Targeted Therapy
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Polyglycolic Acid / administration & dosage
  • Polyglycolic Acid / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • T-Lymphocytes, Cytotoxic / drug effects
  • T-Lymphocytes, Cytotoxic / immunology

Substances

  • Cancer Vaccines
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid