Novel nanohydrogel of hyaluronic acid loaded with quercetin alone and in combination with temozolomide as new therapeutic tool, CD44 targeted based, of glioblastoma multiforme

Manlio Barbarisi, Rosario Vincenzo Iaffaioli, Emilia Armenia, Luigi Schiavo, Gabriele De Sena, Salvatore Tafuto, Alfonso Barbarisi, Vincenzo Quagliariello

Research output: Contribution to journalArticlepeer-review

Abstract

Glioblastoma multiforme is the most common and aggressive primary brain cancer with only ∼3% of patients surviving more than 3 years from diagnosis. Several mechanisms are involved in drug and radiation resistance to anticancer treatments and among them one of the most important factors is the tumor microenvironment status, characterized by cancer cell hypersecretion of interleukins and cytokines. The aim of our research was the synthesis of a nanocarrier of quercetin combined with temozolomide, to enhance the specificity and efficacy of this anticancer drug commonly used in glioblastoma treatment. The nanohydrogel increased the internalization and cytotoxicity of quercetin in human glioblastoma cells and, when co-delivered with temozolomide, contribute to an improved anticancer effect. The nanohydrogel loaded with quercetin had the ability to recognize CD44 receptor, a brain cancer cell marker, through an energy and caveolae dependent mechanism of internalization. Moreover, nanohydrogel of quercetin was able to reduce significantly IL-8, IL-6, and VEGF production in pro-inflammatory conditions with interesting implications on the mechanism of glioblastoma cells drug resistance. In summary, novel CD44 targeted polymeric based nanocarriers appear to be proficient in mediating site-specific delivery of quercetin via CD44 receptor in glioblastoma cells. This targeted therapy lead to an improved therapeutic efficacy of temozolomide by modulating the brain tumor microenvironment.

Original languageEnglish
Pages (from-to)6550-6564
Number of pages15
JournalJournal of Cellular Physiology
Volume233
Issue number10
DOIs
Publication statusPublished - Oct 1 2018

Keywords

  • CD44
  • glioblastoma multiforme
  • hyaluronic acid
  • nanohydrogel
  • quercetin
  • temozolomide

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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