TY - JOUR
T1 - Folic acid-functionalized niosomal nanoparticles for selective dual-drug delivery into breast cancer cells
T2 - an in-vitro investigation
AU - Akbarzadeh, Iman
AU - Tavakkoli Yaraki, Mohammad
AU - Ahmadi, Saeedeh
AU - Chiani, Mohsen
AU - Nourouzian, Dariush
PY - 2020/9
Y1 - 2020/9
N2 - In this study, a folic acid-functionalized niosome was formulated and loaded with letrozole and curcumin as a promising drug carrier system for chemotherapy of the breast cancer cells. The formulation process was optimized by varying the type of Span 80 and total lipid to drug ratio, where Span 80 and lipid to drug molar ratio of 10 resulted in the niosomes with maximum encapsulation of both drugs but minimum size. The developed niosomal formulation showed a great storage stability up to one month with the small changes in drug encapsulation efficiency and size during the storage. In addition, they showed a pH-dependent release behaviour with slow drug release at physiological pH (7.4) while considerable drug release in acidic conditions (pH = 3), making it a promising candidate for breast cancer treatment. The cytotoxicity study shows the niosomal formulation has high biocompatibility with HEK-293 healthy cells, while having remarkable inhibitory effects on MCF-7 and MDA-MB-231 breast cancer cells due to the presence of folic acid in formulation, and in turn, selective internalization of the as-developed nanocarrier through folate receptor-mediated endocytosis. The double drug-loaded niosomes affect the gene expression by studied breast cancer cell lines; down-regulates the expression of Bcl2, cyclin D, and cyclin E genes while they up-regulate the expression of p53, Bax, caspase-3, and caspase-9 genes. The flow cytometry results showed that letrozole/curcumin-loaded niosomes enhanced the apoptosis rate in both MCF-7 and MDA-MB-231 cells compared to the mixture of letrozole and curcumin, which was due to the synergic effect between the two drugs as well as higher cell uptake by niosomal formulation. The findings of our study show the importance of developing highly biocompatible niosomal formulations in the future of nanomedicine that enables the co-delivery of two hydrophobic drugs into the cancer cells improves the efficiency of chemotherapy due to the synergic effect between the drugs.
AB - In this study, a folic acid-functionalized niosome was formulated and loaded with letrozole and curcumin as a promising drug carrier system for chemotherapy of the breast cancer cells. The formulation process was optimized by varying the type of Span 80 and total lipid to drug ratio, where Span 80 and lipid to drug molar ratio of 10 resulted in the niosomes with maximum encapsulation of both drugs but minimum size. The developed niosomal formulation showed a great storage stability up to one month with the small changes in drug encapsulation efficiency and size during the storage. In addition, they showed a pH-dependent release behaviour with slow drug release at physiological pH (7.4) while considerable drug release in acidic conditions (pH = 3), making it a promising candidate for breast cancer treatment. The cytotoxicity study shows the niosomal formulation has high biocompatibility with HEK-293 healthy cells, while having remarkable inhibitory effects on MCF-7 and MDA-MB-231 breast cancer cells due to the presence of folic acid in formulation, and in turn, selective internalization of the as-developed nanocarrier through folate receptor-mediated endocytosis. The double drug-loaded niosomes affect the gene expression by studied breast cancer cell lines; down-regulates the expression of Bcl2, cyclin D, and cyclin E genes while they up-regulate the expression of p53, Bax, caspase-3, and caspase-9 genes. The flow cytometry results showed that letrozole/curcumin-loaded niosomes enhanced the apoptosis rate in both MCF-7 and MDA-MB-231 cells compared to the mixture of letrozole and curcumin, which was due to the synergic effect between the two drugs as well as higher cell uptake by niosomal formulation. The findings of our study show the importance of developing highly biocompatible niosomal formulations in the future of nanomedicine that enables the co-delivery of two hydrophobic drugs into the cancer cells improves the efficiency of chemotherapy due to the synergic effect between the drugs.
KW - Niosome
KW - Letrozole
KW - Curcumin
KW - Breast cancer
KW - Anticancer
UR - http://www.scopus.com/inward/record.url?scp=85090303513&partnerID=8YFLogxK
U2 - 10.1016/j.apt.2020.08.011
DO - 10.1016/j.apt.2020.08.011
M3 - Article
SN - 0921-8831
VL - 31
SP - 4064
EP - 4071
JO - Advanced Powder Technology
JF - Advanced Powder Technology
IS - 9
ER -