Loading diltiazem onto surface-modified nanostructured lipid carriers to evaluate its apoptotic, cytotoxic, and inflammatory effects on human breast cancer cells

Abstract

<p>The main goal of cancer treatment is to ensure that the drug reaches the tumor tissue and to reduce the side effects of the drug. This study was conducted to synthesize a novel nanostructured lipid carrier modified with chitosan-folate to deliver diltiazem to cancer cell lines and to evaluate its anticancer effect. Dynamic light scattering (DLS), field emission scanning electron microscopy (FESEM), and Fourier transform infrared spectrometer (FTIR) methods were used to characterize the nanoparticles. The cytotoxicity effect on cancer cell lines variants was measured. Flow cytometry was used for cell cycle analysis, and reverse transcription polymerase chain reaction (RT-PCR) was performed to assess the induction of apoptosis. The inflammatory effects were evaluated by molecular analysis, and the 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid, 2,2-Diphenyl-1-picrylhydrazyl, and Ferric reducing antioxidant power methods were used to measure the antioxidant power of the nanoparticles. The results reported the mean of the real and hydrodynamic diameter of the nanoparticles as 87.7 and 249 nm, respectively, and the encapsulation efficiency of diltiazem was reported to be 86.6%. The cytotoxicity results revealed that the breast cancer cells were more sensitive to treatment, with a median concentration of 33.5µg/ml. Additionally, the nanoparticle treatment led to the arrest of cells in the SubG1 phase while increasing the expression of caspases 3 and 9, which indicates the activation of the internal pathway of apoptosis. Additionally, the increase in the expression of interleukins 6 and 10 suggests an effect of the nanoparticles on inflammation. In addition, the ability to inhibit 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid and 2,2-Diphenyl-1-picrylhydrazyl free radicals with an average concentration of 577, which is more significant than 1000 µg/ml, and the ability of the nanoparticles to reduce iron ions confirmed the antioxidant effect of diltiazem-loaded nanostructured lipid carriers. These results suggest that the nanoparticles have an excellent potential to treat breast cancer.</p>