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 journalArticle

7 Citations (Scopus)

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

Fingerprint

temozolomide
Quercetin
Hyaluronic Acid
Glioblastoma
Brain Neoplasms
Brain
Tumor Microenvironment
Drug Resistance
Tumors
Cells
Pharmaceutical Preparations
Therapeutics
Caveolae
Interleukins
Cytotoxicity
Interleukin-8
Vascular Endothelial Growth Factor A
Interleukin-6
Radiation
Cytokines

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Novel nanohydrogel of hyaluronic acid loaded with quercetin alone and in combination with temozolomide as new therapeutic tool, CD44 targeted based, of glioblastoma multiforme. / Barbarisi, Manlio; Iaffaioli, Rosario Vincenzo; Armenia, Emilia; Schiavo, Luigi; De Sena, Gabriele; Tafuto, Salvatore; Barbarisi, Alfonso; Quagliariello, Vincenzo.

In: Journal of Cellular Physiology, Vol. 233, No. 10, 01.10.2018, p. 6550-6564.

Research output: Contribution to journalArticle

Barbarisi, Manlio ; Iaffaioli, Rosario Vincenzo ; Armenia, Emilia ; Schiavo, Luigi ; De Sena, Gabriele ; Tafuto, Salvatore ; Barbarisi, Alfonso ; Quagliariello, Vincenzo. / Novel nanohydrogel of hyaluronic acid loaded with quercetin alone and in combination with temozolomide as new therapeutic tool, CD44 targeted based, of glioblastoma multiforme. In: Journal of Cellular Physiology. 2018 ; Vol. 233, No. 10. pp. 6550-6564.
@article{0e0b4cecd647489bb6a3c2c4cc9c3a41,
title = "Novel nanohydrogel of hyaluronic acid loaded with quercetin alone and in combination with temozolomide as new therapeutic tool, CD44 targeted based, of glioblastoma multiforme",
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.",
keywords = "CD44, glioblastoma multiforme, hyaluronic acid, nanohydrogel, quercetin, temozolomide",
author = "Manlio Barbarisi and Iaffaioli, {Rosario Vincenzo} and Emilia Armenia and Luigi Schiavo and {De Sena}, Gabriele and Salvatore Tafuto and Alfonso Barbarisi and Vincenzo Quagliariello",
year = "2018",
month = "10",
day = "1",
doi = "10.1002/jcp.26238",
language = "English",
volume = "233",
pages = "6550--6564",
journal = "Journal of cellular and comparative physiology",
issn = "0021-9541",
publisher = "Wiley-Liss Inc.",
number = "10",

}

TY - JOUR

T1 - Novel nanohydrogel of hyaluronic acid loaded with quercetin alone and in combination with temozolomide as new therapeutic tool, CD44 targeted based, of glioblastoma multiforme

AU - Barbarisi, Manlio

AU - Iaffaioli, Rosario Vincenzo

AU - Armenia, Emilia

AU - Schiavo, Luigi

AU - De Sena, Gabriele

AU - Tafuto, Salvatore

AU - Barbarisi, Alfonso

AU - Quagliariello, Vincenzo

PY - 2018/10/1

Y1 - 2018/10/1

N2 - 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.

AB - 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.

KW - CD44

KW - glioblastoma multiforme

KW - hyaluronic acid

KW - nanohydrogel

KW - quercetin

KW - temozolomide

UR - http://www.scopus.com/inward/record.url?scp=85045234880&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85045234880&partnerID=8YFLogxK

U2 - 10.1002/jcp.26238

DO - 10.1002/jcp.26238

M3 - Article

AN - SCOPUS:85045234880

VL - 233

SP - 6550

EP - 6564

JO - Journal of cellular and comparative physiology

JF - Journal of cellular and comparative physiology

SN - 0021-9541

IS - 10

ER -