Hyaluronic Acid Nanohydrogel Loaded With Quercetin Alone or in Combination to a Macrolide Derivative of Rapamycin RAD001 (Everolimus) as a New Treatment for Hormone-Responsive Human Breast Cancer

V. Quagliariello, R.V. Iaffaioli, E. Armenia, O. Clemente, M. Barbarisi, G. Nasti, M. Berretta, A. Ottaiano, A. Barbarisi

Research output: Contribution to journalArticlepeer-review

Abstract

The aim of this study is based on the evaluation of anticancer, anti-inflammatory activities, and cellular uptake of hyaluronic acid nanohydrogel of quercetin tested alone and in combination to a macrolide derivative of rapamycin RAD001 (everolimus) on hormone-responsive breast cancer cell line MCF-7. Biological investigations were focused on the receptor mediated cellular internalization of the nanohydrogel and its abilities to reduce secretion of several cytokines (IL-8, IL-6, IL-19), VEGF, and metalloproteases (MMP-2, MMP-9) under pro-inflammatory conditions. Nanohydrogel show a CD44 dependent endocytosis with evident time dependent cytoplasmatic accumulation with abilities to reduce secretion of all cytokines of ∼60% compared to untreated cells. Combination of formulated quercetin and everolimus leads to a synergistic cytotoxic effects with a Combination Index of 0.38. These results highlights the importance of synergistic effect of the hyaluronic acid nanohydrogel of quercetin with everolimus in the regulation of human breast cancer cell proliferation and emphasize the antitumor and anti-inflammatory properties of the nanocarrier. J. Cell. Physiol. 232: 2063–2074, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Original languageEnglish
Pages (from-to)2063-2074
Number of pages12
JournalJournal of Cellular Physiology
Volume232
Issue number8
DOIs
Publication statusPublished - 2017

Keywords

  • everolimus
  • gelatinase A
  • gelatinase B
  • Hermes antigen
  • hyaluronic acid
  • interleukin 19
  • interleukin 6
  • interleukin 8
  • messenger RNA
  • nanocarrier
  • nitric oxide
  • nitric oxide synthase
  • quercetin
  • reactive oxygen metabolite
  • toll like receptor 4
  • vasculotropin
  • antiinflammatory agent
  • antineoplastic agent
  • CD44 protein, human
  • drug carrier
  • drug combination
  • hydrogel
  • interleukin derivative
  • MMP2 protein, human
  • MMP9 protein, human
  • nanoparticle
  • vasculotropin A
  • VEGFA protein, human
  • antiinflammatory activity
  • antioxidant activity
  • apoptosis
  • Article
  • breast cancer
  • cell death
  • cell proliferation
  • cell viability
  • cellular secretion
  • controlled study
  • cytokine release
  • cytoplasm
  • drug bioavailability
  • drug cytotoxicity
  • drug potentiation
  • endocytosis
  • human
  • human cell
  • hydrodynamics
  • IC50
  • internalization
  • MCF-7 cell line
  • nanohydrogel
  • particle size
  • physical chemistry
  • priority journal
  • tumor microenvironment
  • upregulation
  • Breast Neoplasms
  • cell survival
  • chemistry
  • dose response
  • drug effects
  • drug formulation
  • female
  • metabolism
  • necrosis
  • Neoplasms, Hormone-Dependent
  • pathology
  • signal transduction
  • Anti-Inflammatory Agents
  • Antigens, CD44
  • Antineoplastic Combined Chemotherapy Protocols
  • Apoptosis
  • Cell Survival
  • Dose-Response Relationship, Drug
  • Drug Carriers
  • Drug Combinations
  • Drug Compounding
  • Drug Synergism
  • Everolimus
  • Female
  • Humans
  • Hyaluronic Acid
  • Hydrogels
  • Interleukins
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • MCF-7 Cells
  • Nanoparticles
  • Necrosis
  • Quercetin
  • Reactive Oxygen Species
  • Signal Transduction
  • Vascular Endothelial Growth Factor A

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