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 language | English |
|---|---|
| Pages (from-to) | 6550-6564 |
| Number of pages | 15 |
| Journal | Journal of Cellular Physiology |
| Volume | 233 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - Oct 1 2018 |
Fingerprint
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 journal › Article
}
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 -