Enhanced anti-tumor activity in mice with temozolomide-resistant human glioblastoma cell line-derived xenograft using sn-38-incorporated polymeric microparticle

Tao Chieh Yang, Shih Jung Liu, Wei Lun Lo, Shu Mei Chen, Ya Ling Tang, Yuan Yun Tseng

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Glioblastoma multiforme (GBM) has remained one of the most lethal and challenging cancers to treat. Previous studies have shown encouraging results when irinotecan was used in combination with temozolomide (TMZ) for treating GBM. However, irinotecan has a narrow therapeutic index: a slight dose increase in irinotecan can induce toxicities that outweigh its therapeutic benefits. SN-38 is the active metabolite of irinotecan that accounts for both its anti-tumor efficacy and toxicity. In our previous paper, we showed that SN-38 embedded into 50:50 biodegradable poly[(d,l)-lactide-co-glycolide] (PLGA) microparticles (SMPs) provides an efficient delivery and sustained release of SN-38 from SMPs in the brain tissues of rats. These properties of SMPs give them potential for therapeutic application due to their high efficacy and low toxicity. In this study, we tested the anti-tumor activity of SMP-based interstitial chemotherapy combined with TMZ using TMZ-resistant human glioblastoma cell line-derived xenograft models. Our data suggest that treatment in which SMPs are combined with TMZ reduces tumor growth and extends survival in mice bearing xenograft tumors derived from both TMZ-resistant and TMZ-sensitive human glioblastoma cell lines. Our findings demonstrate that combining SMPs with TMZ may have potential as a promising strategy for the treatment of GBM.

Original languageEnglish
Article number5557
JournalInternational journal of molecular sciences
Volume22
Issue number11
DOIs
Publication statusPublished - Jun 1 2021

Keywords

  • Glioblastoma multiforme (GBM)
  • Interstitial chemotherapy
  • Poly[(d,l)-lactide-co-glycolide] (PLGA)
  • SN-38
  • Temozolomide-resistance

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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