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

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 an...

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Main Authors: Vahid Pouresmaeil, Marwa Mawlood Salman Al-zand, Aida Pouresmaeil, Seyedeh Samira Saghravanian, Masoud Homayouni Tabrizi
Format: Article
Language:English
Published: AIMS Press 2024-07-01
Series:AIMS Molecular Science
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Online Access:https://www.aimspress.com/article/doi/10.3934/molsci.2024014?viewType=HTML
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author Vahid Pouresmaeil
Marwa Mawlood Salman Al-zand
Aida Pouresmaeil
Seyedeh Samira Saghravanian
Masoud Homayouni Tabrizi
author_facet Vahid Pouresmaeil
Marwa Mawlood Salman Al-zand
Aida Pouresmaeil
Seyedeh Samira Saghravanian
Masoud Homayouni Tabrizi
author_sort Vahid Pouresmaeil
collection DOAJ
description 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.
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spelling doaj-art-e79440e7f00e4c20a48dd98e6aaded8c2025-08-20T01:47:50ZengAIMS PressAIMS Molecular Science2372-03012024-07-0111323125010.3934/molsci.2024014Loading diltiazem onto surface-modified nanostructured lipid carriers to evaluate its apoptotic, cytotoxic, and inflammatory effects on human breast cancer cellsVahid Pouresmaeil 0Marwa Mawlood Salman Al-zand1Aida Pouresmaeil2Seyedeh Samira Saghravanian3Masoud Homayouni Tabrizi41. Department of Biochemistry, Faculty of Medicine, Mashhad Medical Sciences, Islamic Azad University, Mashhad, Iran2. Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran3. Department of Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran3. Department of Biology, Mashhad Branch, Islamic Azad University, Mashhad, Iran3. Department of Biology, Mashhad Branch, Islamic Azad University, Mashhad, IranThe 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.https://www.aimspress.com/article/doi/10.3934/molsci.2024014?viewType=HTMLdiltiazemnanostructured lipid carriersanti-inflammatory effectapoptosisbreast cancer cells
spellingShingle Vahid Pouresmaeil
Marwa Mawlood Salman Al-zand
Aida Pouresmaeil
Seyedeh Samira Saghravanian
Masoud Homayouni Tabrizi
Loading diltiazem onto surface-modified nanostructured lipid carriers to evaluate its apoptotic, cytotoxic, and inflammatory effects on human breast cancer cells
AIMS Molecular Science
diltiazem
nanostructured lipid carriers
anti-inflammatory effect
apoptosis
breast cancer cells
title Loading diltiazem onto surface-modified nanostructured lipid carriers to evaluate its apoptotic, cytotoxic, and inflammatory effects on human breast cancer cells
title_full Loading diltiazem onto surface-modified nanostructured lipid carriers to evaluate its apoptotic, cytotoxic, and inflammatory effects on human breast cancer cells
title_fullStr Loading diltiazem onto surface-modified nanostructured lipid carriers to evaluate its apoptotic, cytotoxic, and inflammatory effects on human breast cancer cells
title_full_unstemmed Loading diltiazem onto surface-modified nanostructured lipid carriers to evaluate its apoptotic, cytotoxic, and inflammatory effects on human breast cancer cells
title_short Loading diltiazem onto surface-modified nanostructured lipid carriers to evaluate its apoptotic, cytotoxic, and inflammatory effects on human breast cancer cells
title_sort loading diltiazem onto surface modified nanostructured lipid carriers to evaluate its apoptotic cytotoxic and inflammatory effects on human breast cancer cells
topic diltiazem
nanostructured lipid carriers
anti-inflammatory effect
apoptosis
breast cancer cells
url https://www.aimspress.com/article/doi/10.3934/molsci.2024014?viewType=HTML
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