TY - JOUR
T1 - Enhanced anticancer potency by combination chemotherapy of HT-29 cells with biodegradable, pH-sensitive nanoparticles for co-delivery of hydroxytyrosol and doxorubicin
AU - Ahmadi, Elham
AU - Zarghami, Nosratollah
AU - Jafarabadi, Mohammad Asghari
AU - Alizadeh, Leila
AU - Khojastehfard, Mehran
AU - Yamchi, Mohammad Rahmati
AU - Salehi, Roya
N1 - Funding Information:
This study was financially supported by a grant [NO: 71/95 ] from Drug Applied Research Center, Tabriz University of Medical Sciences , Tabriz, Iran. I would also like to thank the Farhad Pouremamali M.Sc. student of medical biotechnology, Abbas Pirpour M.Sc. student of medical biochemistry and Zahra Poursalehi M.Sc. student of medical nanotechnology at Tabriz University of medical sciences, Tabriz, IRAN for their comments and sharing their experiences with us during the course of this research.
Publisher Copyright:
© 2019 Elsevier B.V.
PY - 2019/6
Y1 - 2019/6
N2 - A potential approach for clinical colon cancer therapy is combination chemotherapy. In this study, a biodegradable and pH-responsive nano-carrier was designed for co-delivery of Doxorubicin hydrochloride (DOX) and Hydroxytyrosol (HT) in HT-29 colon cancer cells. For this purpose, Poly (lactide-co-glycolic acid-co-acrylic acid) (PLGA-co-PAA) was synthesized by radical AA telomerization in the presence of mercaptoethanol (ME), followed by the ring-opening polymerization (ROP) of lactide and glycolide in the presence of PAA-OH as a chain transfer agent. Nanoparticles with homogeneous spherical morphology and an average diameter of around 18 nm were obtained; cellular uptake of DOX@HT-loaded nanoparticles was more than 94%. Cell cycle analysis and DAPI staining results revealed a high amount of apoptosis on HT-29 cancer cells treated with the dual drug-loaded nanoparticles in comparison to free drugs and single drug-loaded nano-formulations. RT-PCR analysis indicated that the expression levels of hTERT, CREB1 and CREB2 genes were significantly down-regulated in the presence of nano-encapsulated drugs versus free drugs in the HT-29 cell line. Moreover, results revealed that DOX@HT NPs inhibited gene expression more efficiently than single forms. All these results confirmed that these pH-responsive biodegradable nanoparticles are suitable for combination chemotherapy and further in vivo studies in future.
AB - A potential approach for clinical colon cancer therapy is combination chemotherapy. In this study, a biodegradable and pH-responsive nano-carrier was designed for co-delivery of Doxorubicin hydrochloride (DOX) and Hydroxytyrosol (HT) in HT-29 colon cancer cells. For this purpose, Poly (lactide-co-glycolic acid-co-acrylic acid) (PLGA-co-PAA) was synthesized by radical AA telomerization in the presence of mercaptoethanol (ME), followed by the ring-opening polymerization (ROP) of lactide and glycolide in the presence of PAA-OH as a chain transfer agent. Nanoparticles with homogeneous spherical morphology and an average diameter of around 18 nm were obtained; cellular uptake of DOX@HT-loaded nanoparticles was more than 94%. Cell cycle analysis and DAPI staining results revealed a high amount of apoptosis on HT-29 cancer cells treated with the dual drug-loaded nanoparticles in comparison to free drugs and single drug-loaded nano-formulations. RT-PCR analysis indicated that the expression levels of hTERT, CREB1 and CREB2 genes were significantly down-regulated in the presence of nano-encapsulated drugs versus free drugs in the HT-29 cell line. Moreover, results revealed that DOX@HT NPs inhibited gene expression more efficiently than single forms. All these results confirmed that these pH-responsive biodegradable nanoparticles are suitable for combination chemotherapy and further in vivo studies in future.
KW - Biodegradable polymer
KW - Colon cancer
KW - Combination therapy
KW - Hydroxytyrosol
KW - Surface modification
UR - https://www.scopus.com/pages/publications/85064497742
U2 - 10.1016/j.jddst.2019.03.003
DO - 10.1016/j.jddst.2019.03.003
M3 - Article
AN - SCOPUS:85064497742
SN - 1773-2247
VL - 51
SP - 721
EP - 735
JO - Journal of Drug Delivery Science and Technology
JF - Journal of Drug Delivery Science and Technology
ER -
SDG 3 Good Health and Well-being