LRP1-mediated pH-sensitive polymersomes facilitate combination therapy of glioblastoma in vitro and in vivo

J Nanobiotechnology. 2021 Jan 22;19(1):29. doi: 10.1186/s12951-020-00751-x.

Abstract

Background: Glioblastoma (GBM) is the most invasive primary intracranial tumor, and its effective treatment is one of the most daunting challenges in oncology. The blood-brain barrier (BBB) is the main obstacle that prevents the delivery of potentially active therapeutic compounds. In this study, a new type of pH-sensitive polymersomes has been designed for glioblastoma therapy to achieve a combination of radiotherapy and chemotherapy for U87-MG human glioblastoma xenografts in nude mice and significantly increased survival time.

Results: The Au-DOX@PO-ANG has a good ability to cross the blood-brain barrier and target tumors. This delivery system has pH-sensitivity and the ability to respond to the tumor microenvironment. Gold nanoparticles and doxorubicin are designed as a complex drug. This type of complex drug improve the radiotherapy (RT) effect of glioblastoma. The mice treated with Au-DOX@PO-ANG NPs have a significant reduction in tumor volume.

Conclusion: In summary, a new pH-sensitive drug delivery system was fabricated for the treatment of glioblastoma. The new BBB-traversing drug delivery system potentially represents a novel approach to improve the effects of the treatment of intracranial tumors and provides hope for glioblastoma treatment.

Keywords: Brain-targeting; Combination therapy; Glioblastoma; Polymersomes; pH-sensitive.

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / administration & dosage*
  • Antibiotics, Antineoplastic / pharmacokinetics
  • Antibiotics, Antineoplastic / therapeutic use
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Brain Neoplasms / therapy*
  • Cell Line, Tumor
  • Chemoradiotherapy
  • Delayed-Action Preparations / chemistry
  • Delayed-Action Preparations / metabolism*
  • Doxorubicin / administration & dosage*
  • Doxorubicin / pharmacokinetics
  • Doxorubicin / therapeutic use
  • Drug Delivery Systems
  • Female
  • Glioblastoma / metabolism
  • Glioblastoma / pathology
  • Glioblastoma / therapy*
  • Gold / chemistry
  • Humans
  • Hydrogen-Ion Concentration
  • Low Density Lipoprotein Receptor-Related Protein-1 / metabolism*
  • Metal Nanoparticles / chemistry
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Peptides / chemistry
  • Peptides / metabolism
  • Tumor Microenvironment / drug effects

Substances

  • Angiopep-2
  • Antibiotics, Antineoplastic
  • Delayed-Action Preparations
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Peptides
  • Gold
  • Doxorubicin