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.
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.
Department of Abdominal Oncology, National Cancer Institute, IRCCS-Foundation G. Pascale, Naples, Italy.|Department of Anaesthesiological, Surgical and Emergency Sciences, Second University of Naples, Naples, Italy.|ASMO (Association for Multidisciplinary Studies in Oncology) and Mediterranean Diet, Naples, Italy.
Vincenzo
V
Quagliariello
Department of Abdominal Oncology, National Cancer Institute, IRCCS-Foundation G. Pascale, Naples, Italy.|ASMO (Association for Multidisciplinary Studies in Oncology) and Mediterranean Diet, Naples, Italy.
Rosario Vincenzo
RV
Iaffaioli
Department of Anaesthesiological, Surgical and Emergency Sciences, Second University of Naples, Naples, Italy.
Emilia
E
Armenia
Department of Anaesthesiological, Surgical and Emergency Sciences, Second University of Naples, Naples, Italy.
Ottavia
O
Clemente
Department of Medical, Surgical, Neurological, Metabolic and Aging Sciences, Second University of Naples, Naples, Italy.
Manlio
M
Barbarisi
Department of Abdominal Oncology, National Cancer Institute, IRCCS-Foundation G. Pascale, Naples, Italy.
Guglielmo
G
Nasti
Department of Medical Oncology, National Cancer Institute, Aviano (PN), Italy.
Massimiliano
M
Berretta
Department of Abdominal Oncology, National Cancer Institute, IRCCS-Foundation G. Pascale, Naples, Italy.
Alessandro
A
Ottaiano
Department of Anaesthesiological, Surgical and Emergency Sciences, Second University of Naples, Naples, Italy.
Alfonso
A
Barbarisi
D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D004338:Drug Combinations; D004339:Drug Compounding; D004357:Drug Synergism; D000068338:Everolimus / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000737:chemistry / Q000494:pharmacology*; D020100:Hydrogels; D007378:Interleukins / Q000378:metabolism; D061986:MCF-7 Cells; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D053758:Nanoparticles; D009336:Necrosis; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011794:Quercetin / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D000893:Anti-Inflammatory Agents; C497483:CD44 protein, human; D004337:Drug Carriers; D004338:Drug Combinations; D018960:Hyaluronan Receptors; D020100:Hydrogels; D007378:Interleukins; D017382:Reactive Oxygen Species; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D006820:Hyaluronic Acid; D000068338:Everolimus; D011794:Quercetin; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9