Biodegradable hybrid-structured nanofibrous membrane supported chemoprotective gene therapy enhances chemotherapy tolerance and efficacy in malignant glioma rats

Shih Jung Liu, Tao Chieh Yang, Shung Tai Yang, Ying Chun Chen, Yuan Yun Tseng

Research output: Contribution to journalArticle

2 Citations (Scopus)


Chemotherapy is ineffective for treating malignant glioma (MG) because of the low therapeutic levels of pharmaceuticals in tumour tissues and the well-known tumour resistance. The resistance to alkylators is modulated by the DNA repair protein O6-alkylguanine-DNA alkyltransferase (AGT). O6-benzylguanine (O6-BG) can irreversibly inactivate AGT by competing with O6-methylguanine and has been confirmed to increase the therapeutic activity of alkylators. We developed hybrid-structured poly[(d,l)-lactide-co-glycolide] nanofibrous membranes (HSNMs) that enable the sequential and sustained release of O6-BG and two alkylators (carmustine and temozolomide [TMZ]). HSNMs were surgically instilled into the cerebral cavity of pathogen-free rats and F98 glioma-bearing rats. The release behaviours of loaded drugs were quantified by using high-performance liquid chromatography. The treatment results were compared with the rats treated with intraperitoneal injection of O6-BG combined with surgical implantation of carmustine wafer and oral TMZ. The HSNMs revealed a sequential drug release behaviour with the elution of high drug concentrations of O6-BG in the early phase, followed by high levels of two alkylators. All drug concentrations remained high for over 14 weeks. Tumour growth was slower and the mean survival time was significantly prolonged in the HSNM-treated group. Biodegradable HSNMs can enhance therapeutic efficacy and prevent toxic systemic effects.

Original languageEnglish
Pages (from-to)1-12
Number of pages12
JournalArtificial Cells, Nanomedicine and Biotechnology
Publication statusAccepted/In press - Apr 14 2018



  • alkylguanine-DNA alkyltransferase (AGT)
  • chemo-resistance
  • malignant glioma
  • Nanofibrous membrane
  • O-benzylguanine (O-BG)
  • poly[(d,l)-lactide-co-glycolide] (PLGA)

ASJC Scopus subject areas

  • Biotechnology
  • Medicine (miscellaneous)
  • Biomedical Engineering
  • Pharmaceutical Science

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