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Evaluation of anti-cancer and anti-metastatic effects of folate-PEGylated niosomes for co-delivery of letrozole and ascorbic acid on breast cancer cells

Lookup NU author(s): Dr Yen Nee Tan

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Abstract

© 2022 The Royal Society of Chemistry. Fighting with cancer requires the delivery of different therapeutics to the target cancerous cells by taking advantage of the synergistic effects of complementary medicine. Herein, we present a folate-PEGylated niosome as an efficient nanocarrier for targeted co-delivery of hydrophobic letrozole (L) and hydrophilic ascorbic acid (A) to breast cancer cells. The formulation of the niosomal nanocarrier was optimized by varying the ratio of cholesterol and surfactants to maximize the drug loading and minimize the size of nanocarriers. The optimum drug carriers were further functionalized with folate-PEG molecules to enhance the efficiency of drug delivery to the breast cancer cells and prevent their destruction by macrophages. The as-developed niosomal nanocarriers were comprehensively characterized by different physicochemical techniques such as TEM, XRD, FTIR, etc. The folate-PEGylated niosomes containing both letrozole and ascorbic acid (i.e., folate-PEGylated LA-niosomes) showed excellent colloidal stability and high biocompatibility with normal cells in a cytotoxicity study, while exhibiting significant anticancer and anti-metastatic effects on both MDA-MB-231 and SKBR3 breast cancer cells. Further gene expression studies in these two cancer cells revealed downregulation of Cyclin D, MMP-2 and MMP-9 genes and upregulation of the expression of Caspase-3 and Caspase-9 genes. Flow cytometry studies also confirmed that the folate-PEGylated LA-niosomes can increase the rate of apoptosis in the MDA-MB-231 and SKBR3 cancer cells, showing synergistic effects between the two complementary anticancer drugs in the treatment process. This study demonstrated the promising use of the cancer cell-specific folate-PEGylated LA-niosomes as highly effective multiple drug delivery nanocarriers for cancer treatment due to their increased drug efficacy and reduced side effects of chemotherapy.


Publication metadata

Author(s): Bourbour M, Khayam N, Noorbazargan H, Tavakkoli Yaraki M, Asghari Lalami Z, Akbarzadeh I, Eshrati Yeganeh F, Dolatabadi A, Mirzaei Rad F, Tan YN

Publication type: Article

Publication status: Published

Journal: Molecular Systems Design and Engineering

Year: 2022

Pages: Epub ahead of print

Online publication date: 25/05/2022

Acceptance date: 18/05/2022

ISSN (electronic): 2058-9689

Publisher: Royal Society of Chemistry

URL: https://doi.org/10.1039/d2me00024e

DOI: 10.1039/d2me00024e


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