Iguratimod encapsulated PLGA-NPs improves therapeutic outcome in glioma, glioma stem-like cells and temozolomide resistant glioma cells

Nanomedicine. 2019 Nov:22:102101. doi: 10.1016/j.nano.2019.102101. Epub 2019 Oct 22.

Abstract

Glioma is the most common neoplasm of the central nervous system, with the highest mortality rate. The present study was designed to examine the therapeutic effect of Iguratimod (IGU) encapsulated-poly (lactic-co-glycolic acid) PLGA nanoparticles (IGU-PLGA-NPs), which showed inhibition of glioma cells proliferation both in vitro and in vivo. IGU encapsulated in PLGA nanoparticles with an average size of 100-200 nm was prepared using modified double-emulsion (W1/O/W2) method. Cell Counting Kit-8 (CCK-8) analysis of Glioma cancer cells and glioma stem-like cells (GSCs) demonstrated significant inhibition of their growth treated with IGU-PLGA-NPs. IGU-PLGA-NPs inhibit migration in glioma cells as well as tumor sphere formation in GSCs. Treatment with IGU-PLGA-NPs showed a significant decrease in tumor growth through the apoptotic pathway in mice model without any visible organ toxicity and it can successfully cross the blood brain barrier (BBB). Most Importantly, IGU-PLGA-NPs significantly depleted growth of U251 Temozolomide-resistant (U251TMZ-R) cells.

Keywords: Apoptosis; Cancer; Glioma; Iguratimod; PLGA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / metabolism
  • Blood-Brain Barrier / pathology
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Self Renewal / drug effects
  • Chromones / pharmacology
  • Chromones / therapeutic use*
  • Drug Resistance, Neoplasm* / drug effects
  • Glioma / drug therapy*
  • Glioma / pathology
  • Humans
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nanoparticles / chemistry*
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / pathology*
  • Polylactic Acid-Polyglycolic Acid Copolymer / chemistry*
  • Spheroids, Cellular / drug effects
  • Spheroids, Cellular / pathology
  • Sulfonamides / pharmacology
  • Sulfonamides / therapeutic use*
  • Temozolomide / pharmacology
  • Temozolomide / therapeutic use*
  • Treatment Outcome

Substances

  • Chromones
  • Sulfonamides
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • iguratimod
  • Temozolomide