Targeted Imaging and Chemo-Phototherapy of Brain Cancer by a Multifunctional Drug Delivery System

Macromol Biosci. 2015 Nov;15(11):1571-85. doi: 10.1002/mabi.201500091. Epub 2015 Jul 14.

Abstract

The aim of this study was to develop multifunctional poly lactide-co-glycolide (PLGA) nanoparticles with the ability to simultaneously deliver indocyanine green (ICG) and docetaxel (DTX) to the brain by surface decoration with the brain-targeting peptide angiopep-2 to achieve combined chemo-phototherapy for glioma under near-infrared (NIR) imaging. ICG was selected as a near-infrared imaging and phototherapy agent and DTX was employed as a chemotherapeutic agent. ICG and DTX were simultaneously incorporated into PLGA nanoparticles with higher stability. These nanoparticles were further decorated with angiopep-2 via the outer maleimide group of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethyleneglycol)-2000]-maleinimide incorporated in the nanoparticles. The NIR image-guided chemo-phototherapy of the angiopep-2 modified PLGA/DTX/ICG nanoparticles (ANG/PLGA/DTX/ICG NPs) not only highly induced U87MG cell death in vitro, but also efficiently prolonged the life span of the brain orthotopic U87MG glioma xenograft-bearing mice in vivo. Thus, this study suggests that ANG/PLGA/DTX/ICG NPs have the potential for combinatorial chemotherapy and phototherapy for glioma.

Keywords: PLGA nanoparticles; angiopep-2; chemo-phototherapy; glioma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Neoplasms* / drug therapy
  • Brain Neoplasms* / metabolism
  • Brain Neoplasms* / pathology
  • Cell Line, Tumor
  • Docetaxel
  • Drug Delivery Systems
  • Glioma* / drug therapy
  • Glioma* / metabolism
  • Glioma* / pathology
  • Humans
  • Lactic Acid* / chemistry
  • Lactic Acid* / pharmacokinetics
  • Lactic Acid* / pharmacology
  • Mice
  • Mice, Nude
  • Nanoparticles / chemistry*
  • Optical Imaging / methods*
  • Peptides* / chemistry
  • Peptides* / pharmacokinetics
  • Peptides* / pharmacology
  • Photochemotherapy / methods*
  • Polyglycolic Acid* / chemistry
  • Polyglycolic Acid* / pharmacokinetics
  • Polyglycolic Acid* / pharmacology
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Taxoids* / chemistry
  • Taxoids* / pharmacokinetics
  • Taxoids* / pharmacology
  • Xenograft Model Antitumor Assays

Substances

  • Angiopep-2
  • Peptides
  • Taxoids
  • Docetaxel
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid