Abstract
Combination chemotherapy by means of two or more drugs is prone to suppressing or discouraging the inception of multidrug resistance, exploiting the fact that diverse drugs act in different points of the cellular cycle of amplifying tumor cells. For example, the combination of gemcitabine (GMC) with quercetin (QCT) showed a synergistic effect in inhibiting the migration of pancreatic cancer cells. Consequently, herein GMC and QCT have been loaded within biodegradable nanoparticles (NPs) based on poly(lactic-co-glycolic acid), externally decorated with hyaluronic acid (HA; viz., PPHA NPs), which plays a major role in drug targeting to tumors due to its ability to specifically interact with CD44 receptor, that is overexpressed in many tumors. The produced HA-decorated NPs loaded with GMC and QCT showed an improved cytotoxicity and cellular uptake toward two cell lines of pancreatic ductal adenocarcinoma, namely Mia-PaCa-2 and PANC-1, compared with both the bare drugs and the drugs loaded in NPs which do not expose HA on the surface. HA-decorated NPs were also able to improve the anti-inflammatory properties of QCT, therefore leading to a decrease of interleukin cellular levels in both cell lines, preliminarily stimulated with lipopolysaccharides. This result is of special interest also considering the crucial role of interleukins in progression, metastatic processes, and drug resistance of human pancreas cancer cells.
| Original language | English |
|---|---|
| Journal | Journal of Cellular Physiology |
| DOIs | |
| Publication status | Published - 2019 |
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Keywords
- CD44
- gemcitabine
- nanoparticles
- pancreatic cancer
- quercetin
ASJC Scopus subject areas
- Physiology
- Clinical Biochemistry
- Cell Biology
Cite this
Combination therapy for the treatment of pancreatic cancer through hyaluronic acid-decorated nanoparticles loaded with quercetin and gemcitabine : A preliminary in vitro study. / Serri, Carla; Quagliariello, Vincenzo; Iaffaioli, Rosario Vincenzo; Fusco, Sabato; Botti, Gerardo; Mayol, Laura; Biondi, Marco.
In: Journal of Cellular Physiology, 2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Combination therapy for the treatment of pancreatic cancer through hyaluronic acid-decorated nanoparticles loaded with quercetin and gemcitabine
T2 - A preliminary in vitro study
AU - Serri, Carla
AU - Quagliariello, Vincenzo
AU - Iaffaioli, Rosario Vincenzo
AU - Fusco, Sabato
AU - Botti, Gerardo
AU - Mayol, Laura
AU - Biondi, Marco
PY - 2019
Y1 - 2019
N2 - Combination chemotherapy by means of two or more drugs is prone to suppressing or discouraging the inception of multidrug resistance, exploiting the fact that diverse drugs act in different points of the cellular cycle of amplifying tumor cells. For example, the combination of gemcitabine (GMC) with quercetin (QCT) showed a synergistic effect in inhibiting the migration of pancreatic cancer cells. Consequently, herein GMC and QCT have been loaded within biodegradable nanoparticles (NPs) based on poly(lactic-co-glycolic acid), externally decorated with hyaluronic acid (HA; viz., PPHA NPs), which plays a major role in drug targeting to tumors due to its ability to specifically interact with CD44 receptor, that is overexpressed in many tumors. The produced HA-decorated NPs loaded with GMC and QCT showed an improved cytotoxicity and cellular uptake toward two cell lines of pancreatic ductal adenocarcinoma, namely Mia-PaCa-2 and PANC-1, compared with both the bare drugs and the drugs loaded in NPs which do not expose HA on the surface. HA-decorated NPs were also able to improve the anti-inflammatory properties of QCT, therefore leading to a decrease of interleukin cellular levels in both cell lines, preliminarily stimulated with lipopolysaccharides. This result is of special interest also considering the crucial role of interleukins in progression, metastatic processes, and drug resistance of human pancreas cancer cells.
AB - Combination chemotherapy by means of two or more drugs is prone to suppressing or discouraging the inception of multidrug resistance, exploiting the fact that diverse drugs act in different points of the cellular cycle of amplifying tumor cells. For example, the combination of gemcitabine (GMC) with quercetin (QCT) showed a synergistic effect in inhibiting the migration of pancreatic cancer cells. Consequently, herein GMC and QCT have been loaded within biodegradable nanoparticles (NPs) based on poly(lactic-co-glycolic acid), externally decorated with hyaluronic acid (HA; viz., PPHA NPs), which plays a major role in drug targeting to tumors due to its ability to specifically interact with CD44 receptor, that is overexpressed in many tumors. The produced HA-decorated NPs loaded with GMC and QCT showed an improved cytotoxicity and cellular uptake toward two cell lines of pancreatic ductal adenocarcinoma, namely Mia-PaCa-2 and PANC-1, compared with both the bare drugs and the drugs loaded in NPs which do not expose HA on the surface. HA-decorated NPs were also able to improve the anti-inflammatory properties of QCT, therefore leading to a decrease of interleukin cellular levels in both cell lines, preliminarily stimulated with lipopolysaccharides. This result is of special interest also considering the crucial role of interleukins in progression, metastatic processes, and drug resistance of human pancreas cancer cells.
KW - CD44
KW - gemcitabine
KW - nanoparticles
KW - pancreatic cancer
KW - quercetin
UR - http://www.scopus.com/inward/record.url?scp=85055283642&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85055283642&partnerID=8YFLogxK
U2 - 10.1002/jcp.27297
DO - 10.1002/jcp.27297
M3 - Article
JO - Journal of Cellular Physiology
JF - Journal of Cellular Physiology
SN - 0021-9541
ER -