Abstract
In the present study, a magnetic niosomal nanocarrier for co-delivery of curcumin and letrozole into breast cancer cells has been designed. The magnetic NiCoFe2O4 core was coated by a thin layer of silica, followed by a niosomal structure, allowing us to load letrozole and curcumin into the silica layer and niosomal layer, respectively, and investigate their synergic effects on breast cancer cells. Furthermore, the nanocarriers demonstrated a pH-dependent release due to the niosomal structure at their outer layer, which is a promising behavior for cancer treatment. Additionally, cellular assays revealed that the nanocarriers had low cellular uptake in the case of non-tumorigenic cells (i.e., MCF-10A) and related high viability but high cellular uptake in cancer cell lines (i.e., MDA-MB-231 and SK-BR-3) and related low viability, which is evidenced in their high cytotoxicity against different breast cancer cell lines. The cytotoxicity of the letrozole/curcumin co-loaded nanocarrier is higher than that of the aqueous solutions of both drugs, indicating their enhanced cellular uptake in their encapsulated states. In particular, NiCoFe2O4@L-Silica-L@C-Niosome showed the highest cytotoxicity effects on MDA-MB-231 and SK-BR-3 breast cancer cells. The observed cytotoxicity was due to regulation of the expression levels of the studied genes in breast cancer cells, where downregulation was observed for the Bcl-2, MMP 2, MMP 9, cyclin D, and cyclin E genes while upregulation of the expression of the Bax, caspase-3, and caspase-9 genes was observed. The flow cytometry results also revealed that NiCoFe2O4@L-Silica-L@C-Niosome enhanced the apoptosis rate in both MDA-MB-231 and SK-BR-3 cells compared to the control samples. The findings of our research show the potential of designing magnetic niosomal formulations for simultaneous targeted delivery of both hydrophobic and hydrophilic drugs into cancer cells in order to enhance their synergic chemotherapeutic effects. These results could open new avenues into the future of nanomedicine and the development of theranostic agents.
Highlights
Breast cancer is one of the most common cancers in women
In the MDA-MB-231 and SK-BR-3 cell lines, we found that the expression rates for both cyclin genes were significantly reduced after treatment with NiCoFe2 O4 @L-Silica@C-Niosome
We examined the ability of NiCoFe2 O4 @L-Silica@C-Niosome treatment to induce apoptosis in SK-BR-3 and MDA-MB-231 cells by gene expression
Summary
Breast cancer is one of the most common cancers in women. In 2020, the number of female breast cancer patients increased dramatically, with an estimated 2.3 million new cases, while the fatality rate of this malignant disease was 6.9% [1]. In addition to surgery and radiotherapy, the use of chemotherapy as well as targeted therapy has increased for the treatment of breast cancer, along with the availability of supportive therapies for the management of side effects [2]. To overcome the side effects of chemotherapy, a targeted drug delivery approach using highly biocompatible nanomaterials has received tremendous attention in recent years, whereby the wet synthesis approach allows for stepby-step synthesis of nanocarriers with a controllable size at a large scale and controllable surface functionality to be able to interact with the target tissue [3,4,5,6,7]. A combination of nanocarriers that have potential for delivering both hydrophobic and hydrophilic molecules with nanomaterials that provides the targeted features could be a promising approach for efficient drug delivery [10,11,12]
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