Doxorubicin Loaded in Niosomal Nanoparticles Improved Inhibitory Effect of Free Doxorubicin on Cancer Stem Cell Markers in Human Breast cancer Cells

نویسندگان

1 Department of Biology, Faculty of Science, Shahid Bahonar University of Kerman, Kerman, Iran

2 Herbal and Traditional Medicines Research Center, Kerman University of Medical Sciences, Kerman, Iran

3 Pathology and Stem Cell Research Center, Kerman University of Medical Sciences, Kerman, Iran

4 Department of Biology, Faculty of Science, Shahid Bahonar University of Kerman, Kerman, Iran

doi
10.22034/nmrj.2025.01.005
چکیده

Doxorubicin (DOX) is an effective chemotherapy drug for breast cancer treatment. However, its side effect and breast cancer resistance limit its clinical application. Therefore, drug delivery systems were designed to decrease its side effects and improve therapeutic efficacy. Here, we prepared and characterized DOX-loaded niosomes (Nio-DOX) and evaluated cytotoxicity and inhibitory effect of Nio-DOX on cancer stem cell markers in MCF-7 cells. Noisome were prepared with mixture of nonionic surfactant (Tween 40, span 40) and cholesterol at 50:50 wt/wt % ratio using film hydration method. Characteristics of noisome, including size, zeta potential, morphology, drug entrapment efficiency (EE) and in vitro release behavior were studied. Cytotoxicity against MCF-7 and inhibitory effect on expression of CSC markers were evaluated by MTT assay and Real time PCR. DOX-Nio showed spherical structure with size, zeta potential, and EE values of 67.81 ± 3.25 nm, -3.48 ± 0.16 mV, and 92.03±2.95 %, respectively. The release profiles of DOX-Nio revealed the extended release over of 5 h. The IC50 values of DOX and Nio-DOX were 5.6 and 1.6 Doxorubicin (DOX) is an effective chemotherapy drug for breast cancer treatment. However, its side effect and breast cancer resistance limit its clinical application. Therefore, drug delivery systems were designed to decrease its side effects and improve therapeutic efficacy. Here, we prepared and characterized DOX-loaded niosomes (Nio-DOX) and evaluated cytotoxicity and inhibitory effect of Nio-DOX on cancer stem cell markers in MCF-7 cells. Noisome were prepared with mixture of nonionic surfactant (Tween 40, span 40) and cholesterol at 50:50 wt/wt % ratio using film hydration method. Characteristics of noisome, including size, zeta potential, morphology, drug entrapment efficiency (EE) and in vitro release behavior were studied. Cytotoxicity against MCF-7 and inhibitory effect on expression of CSC markers were evaluated by MTT assay and Real time PCR. DOX-Nio showed spherical structure with size, zeta potential, and EE values of 67.81 ± 3.25 nm, -3.48 ± 0.16 mV, and 92.03±2.95 %, respectively. The release profiles of DOX-Nio revealed the extended release over of 5 h. The IC50 values of DOX and Nio-DOX were 5.6 and 1.6  g/ml after 48h, respectively which show higher cytotoxicity of Nio-DOX against MCF-7. DOX-Nio significantly decreased CD44, CD1133, ALDH1, SOX2 and ABCB1, while free DOX had no significant effect on these markers. The resulting data showed that Nio-DOX has stronger inhibitory effects on MCF-7 viability and expression of CSC markers compared to free drug. Therefore, noisome could be a good carrier system for targeted delivery of the drugs in the treatment of breast cancer.