Esterase-responsive and size-optimized prodrug nanoparticles for effective intracranial drug delivery and glioblastoma treatment

Nanomedicine. 2022 Aug:44:102581. doi: 10.1016/j.nano.2022.102581. Epub 2022 Jul 8.

Abstract

Glioblastoma multiforme (GBM) is the intracranial malignancy with the highest rates of morbidity and mortality. Chemotherapy is often ineffective against GBM due to the presence of the blood-brain barrier (BBB); however, the application of nanotechnology is expected to overcome this limitation. Poly(lactic-co-glycolic acid) (PLGA) is a degradable and nontoxic functional polymer with good biocompatibility that is widely used in the pharmaceutical industry. Previous studies have shown that the ability of PLGA nanoparticles (NPs) to penetrate the BBB is largely determined by their size; however, determination of the optimal PLGA NP size requires further research. Here, we report a tandutinib-based prodrug (proTan), which responds to the GBM microenvironment, that was combined with NPs to overcome the BBB. AMD3100-PLGA NPs loaded with proTan inhibited tumor growth and effectively prolonged the survival of tumor-bearing mice.

Keywords: CXCR4; GBM; PLGA nanoparticle; Prodrug; Tandutinib.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Drug Carriers / therapeutic use
  • Drug Delivery Systems
  • Esterases / therapeutic use
  • Glioblastoma* / drug therapy
  • Glioblastoma* / pathology
  • Lactic Acid
  • Mice
  • Nanoparticles*
  • Polyglycolic Acid
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Prodrugs* / pharmacology
  • Prodrugs* / therapeutic use
  • Tumor Microenvironment

Substances

  • Drug Carriers
  • Prodrugs
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Esterases