OncoTargets and Therapy (Nov 2020)

Local Delivery of Minocycline and Vorinostat Targets the Tumor Microenvironment to Inhibit the Recurrence of Glioma

  • Zhao G,
  • Jia J,
  • Wang L,
  • Zhang Y,
  • Yang H,
  • Lu Y,
  • Yu R,
  • Liu H,
  • Zhu Y

Journal volume & issue
Vol. Volume 13
pp. 11397 – 11409

Abstract

Read online

Gang Zhao,1,* Jun Jia,1,* Lansheng Wang,1,* Yongkang Zhang,1 Han Yang,1 Yang Lu,1 Rutong Yu,1,2 Hongmei Liu,1– 3 Yufu Zhu1,2 1Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou 221002, People’s Republic of China; 2Department of Neurosurgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, People’s Republic of China; 3Department of Neurosurgery, The Third People’s Hospital Affiliated of Xuzhou Medical University, Xuzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yufu Zhu; Hongmei Liu Tel +86 18052268167Email [email protected]; [email protected]: Postoperative recurrence is the main reason for poor clinical outcomes in glioma patients, so preventing tumor recurrence is crucial in the management of gliomas.Methods: In this study, the expression of matrix metalloproteinases (MMPs) in normal tissues was detected via RNA-seq analysis. Glioma cases from the public databases (The Cancer Genome Atlas (TCGA), the Chinese Glioma Genome Atlas (CGGA)) were included in this study. The hydrogel contains minocycline (Mino) and vorinostat (Vor) (G/Mino+Vor) was formed under 365 nm when the photoinitiator was added. High-performance liquid chromatography (HPLC) was used to assess the release of drugs in the G/Mino+Vor hydrogel. An MTT assay was used to explore the biosecurity of GelMA. Immunohistochemistry, ELISA, and TUNEL assays were used to demonstrate the antitumor effect of the G/Mino+Vor hydrogel.Results: We successfully developed a G/Mino+Vor hydrogel. The experiments in vitro and in vivo confirmed the MMPs-responsive delivery of minocycline and vorinostat in hydrogel and the anti-glioma effect on an incomplete tumor operation model, which indicated that the G/Mino+Vor hydrogel effectively inhibited the recurrence of glioma after surgery.Conclusion: In summary, the G/Mino+Vor hydrogel could continuously release drugs and improve the therapy effects against recurrent glioma.Keywords: minocycline, vorinostat, recurrent glioma, hydrogel, tumor microenvironmennt

Keywords