<p>Local Delivery of Minocycline and Vorinostat Targets the Tumor Microenvironment to Inhibit the Recurrence of Glioma</p>

Abstract

Background: 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.

Printing GelMA bioinks: a strategy for building in vitro model to study nanoparticle-based minocycline release and cellular protection under oxidative stress

“…Literature relating to using GelMA to deliver MH has been mostly on direct mixing [38,39], our findings indicate that this approach results in high burst release and lacks sustained-release properties. In addition, the significantly reduced accumulative release from direct mixing groups may account for the oxidation from free radicals residuals of GelMA photocrosslinking.…”

Histone‐deacetylase 8 drives the immune response and the growth of glioma

“…Many epigenetic modifications occur in glioma resulting in substantial molecular heterogeneity that confers advantages for tumor development (Phillips et al, 2020 ). Among the enzymes involved, the histone deacetylases regulate different hallmarks of glioma pathogenesis, such as proliferation, invasiveness, and formation of new vessels (Pastorino et al, 2019 ; Zhao et al, 2020 ). HDACi fascinated researchers in almost all fields of cancer biology: five of them have been approved by FDA for clinical use and many others tentered clinical trials as single agents or in combination therapy for a variety of cancer diseases (Ecker et al, 2013 ; Lee et al, 2015 ).…”

Integrative Analysis of a Novel Eleven-Small Nucleolar RNA Prognostic Signature in Patients With Lower Grade Glioma

“…Local Delivery of vorinostat can alter the tumor microenvironment, thereby inhibiting glioma recurrence (40). Vorinostat can also mediate the regulation of cell cycle regulatory proteins in glioma (41).…”

“…Clinical trials have shown that vorinostat combined with Bevacizumab or Temozolomide can be used in the treatment of glioma ( 33 – 35 ), as well recurrent malignant gliomas ( 36 – 39 ). Local Delivery of vorinostat can alter the tumor microenvironment, thereby inhibiting glioma recurrence ( 40 ). Vorinostat can also mediate the regulation of cell cycle regulatory proteins in glioma ( 41 ).…”