Tumor-derived exosomes reversing TMZ resistance by synergistic drug delivery for glioma-targeting treatment

Colloids Surf B Biointerfaces. 2022 Jul:215:112505. doi: 10.1016/j.colsurfb.2022.112505. Epub 2022 Apr 15.

Abstract

Temozolomide (TMZ), as the first-line chemotherapeutic agent, relies on inducing DNA methylation of O6-guanine for treating glioma. However, the survival time of patients are hardly exceeded 14.5 months, attributing to inevitable drug resistance and systematic toxicity after long-term administration. Herein, reassembly-exosomes (R-EXO) deriving from homologous glioma cells is proposed to carry TMZ and Dihydrotanshinone (DHT) for reversing drug resistance and enhancing lesions-targeted drug delivery, defined as R-EXO-TMZ/DHT (R-EXO-T/D). It is found that R-EXO-T/D share various advantages, including preferable blood-brain barrier (BBB)-penetrating ability with nanomemter size, tumor-homing accumulation with homologous effects, as well as potentiated antitumor activity with overcoming TMZ resistance and triggering immune response. This work develops a new strategy for site-specific drug delivery, showing a promising application of drug compatibility in glioma treatment.

Keywords: Combination therapy; Dihydrotanshinone; Exosome; Immunotherapy; Temozolomide.

MeSH terms

  • Antineoplastic Agents, Alkylating / pharmacology
  • Antineoplastic Agents, Alkylating / therapeutic use
  • Brain Neoplasms* / drug therapy
  • Brain Neoplasms* / pathology
  • Cell Line, Tumor
  • Drug Resistance, Neoplasm
  • Exosomes*
  • Glioma* / pathology
  • Humans
  • Temozolomide / pharmacology
  • Temozolomide / therapeutic use

Substances

  • Antineoplastic Agents, Alkylating
  • Temozolomide