Gastrodin Liposomes Block Crosstalk between Astrocytes and Glioma Cells via Downregulating Cx43 to Improve Antiglioblastoma Efficacy of Temozolomide

Bioconjug Chem. 2024 Sep 18;35(9):1380-1390. doi: 10.1021/acs.bioconjchem.4c00300. Epub 2024 Aug 24.

Abstract

The crosstalk between glioma cells and astrocytes plays a crucial role in developing temozolomide (TMZ) resistance of glioblastomas, together with the existence of the BBB contributing to the unsatisfactory clinical treatment of glioblastomas. Herein, we developed a borneol-modified and gastrodin-loaded liposome (Bo-Gas-LP), with the intent of enhancing the efficacy of TMZ therapy after intranasal administration. The results showed that Bo-Gas-LP improved GL261 cells' sensitivity to TMZ and prolonged survival of GL261-bearing mice by blocking the crosstalk between astrocytes and glioblastoma cells with the decrease of Cx43. Our study showed that intranasal Bo-Gas-LP targeting the crosstalk in glioblastoma microenvironments proposed a promising targeted therapy idea to overcome the current therapeutic limitations of TMZ-resistant glioblastomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Alkylating / pharmacology
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Astrocytes* / drug effects
  • Astrocytes* / metabolism
  • Benzyl Alcohols* / chemistry
  • Benzyl Alcohols* / pharmacology
  • Benzyl Alcohols* / therapeutic use
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Connexin 43* / metabolism
  • Down-Regulation* / drug effects
  • Glioblastoma / drug therapy
  • Glioblastoma / metabolism
  • Glioblastoma / pathology
  • Glioma / drug therapy
  • Glioma / metabolism
  • Glioma / pathology
  • Glucosides* / chemistry
  • Glucosides* / pharmacology
  • Glucosides* / therapeutic use
  • Humans
  • Liposomes* / chemistry
  • Mice
  • Mice, Inbred C57BL
  • Temozolomide* / pharmacology
  • Temozolomide* / therapeutic use

Substances

  • Temozolomide
  • Glucosides
  • Liposomes
  • gastrodin
  • Benzyl Alcohols
  • Connexin 43
  • Antineoplastic Agents, Alkylating