Evaluation of Liposomal and Microbubbles Mediated Delivery of Doxorubicin in Two-Dimensional (2D) and Three-Dimensional (3D) Models for Breast Cancer

Objective:Liposomal cancer treatment strategies are useful in removing the side effects that were the main concern in recent years. In this study, we prepared microbubble (MBs) conjugated with DOX-loaded liposomes (DOX-loaded MBs) and investigated their effectiveness in in vitro breast cancer cells...

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Main Authors: Melek Aydın, Ekrem Özdemir, Zekiye Altun, Sevgi Kılıç, Safiye Aktaş
Format: Article
Language:English
Published: Galenos Publishing House 2021-07-01
Series:European Journal of Breast Health
Subjects:
Online Access: http://www.eurjbreasthealth.com/archives/archive-detail/article-preview/evaluation-of-liposomal-and-microbubbles-mediated-/47936
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author Melek Aydın
Ekrem Özdemir
Zekiye Altun
Sevgi Kılıç
Safiye Aktaş
author_facet Melek Aydın
Ekrem Özdemir
Zekiye Altun
Sevgi Kılıç
Safiye Aktaş
author_sort Melek Aydın
collection DOAJ
description Objective:Liposomal cancer treatment strategies are useful in removing the side effects that were the main concern in recent years. In this study, we prepared microbubble (MBs) conjugated with DOX-loaded liposomes (DOX-loaded MBs) and investigated their effectiveness in in vitro breast cancer cells in two dimensions (2D) and three dimensions (3D).Materials and Methods:With this aim, breast cancer cells with different features (4T1, MDA-MB231, MCF-7) were growth in 2D and 3D dimensions. The cytotoxic and cell death effects under different conditions, durations and doses were evaluated with WST-1, trypan-blue, colony counts. Apoptotic effects were investigated with flow cytometric Annexin-V-PI and immunohistochemical (Ki-67, caspase 3, 8, 9) methods.Results:After free DOX and LipoDOX were applied, the proliferation index of three cell lines reduced. Intrinsic and extrinsic apoptotic pathways were activated in both 2D and 3D models. However, this effect was observed at lower levels in the 3D model due to the difficulty of diffusion of DOX into the spheroids. Additionally, the suitability of the 3D model for breast cancer cells was supported by formation of ductus-like structures and spheroids. Cell deaths were not observed significantly with the DOX-loaded microbubbles due to rising of MBs to the surface and not reaching spheroids held in matrigel of 3D model.Conclusion:DOX and LipoDOX showed anti-proliferative and apoptosis-inducing effects in breast cancer cells. However, these effects indicated variability depending on the cell lines and 2D or 3D model types.
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spelling doaj.art-289a5ddd48294007b239b73a836bddc32023-02-15T16:13:39ZengGalenos Publishing HouseEuropean Journal of Breast Health2587-08312021-07-0117327428210.4274/ejbh.galenos.2021.625513049054Evaluation of Liposomal and Microbubbles Mediated Delivery of Doxorubicin in Two-Dimensional (2D) and Three-Dimensional (3D) Models for Breast CancerMelek Aydın0Ekrem Özdemir1Zekiye Altun2Sevgi Kılıç3Safiye Aktaş4 Department of Basic Oncology, Institute of Oncology, Dokuz Eylül University, İzmir, Turkey Department of Chemical Engineering, İzmir Institute of Technology, İzmir, Turkey Department of Basic Oncology, Institute of Oncology, Dokuz Eylül University, İzmir, Turkey Department of Chemical Engineering, İzmir Institute of Technology, İzmir, Turkey Department of Basic Oncology, Institute of Oncology, Dokuz Eylül University, İzmir, Turkey Objective:Liposomal cancer treatment strategies are useful in removing the side effects that were the main concern in recent years. In this study, we prepared microbubble (MBs) conjugated with DOX-loaded liposomes (DOX-loaded MBs) and investigated their effectiveness in in vitro breast cancer cells in two dimensions (2D) and three dimensions (3D).Materials and Methods:With this aim, breast cancer cells with different features (4T1, MDA-MB231, MCF-7) were growth in 2D and 3D dimensions. The cytotoxic and cell death effects under different conditions, durations and doses were evaluated with WST-1, trypan-blue, colony counts. Apoptotic effects were investigated with flow cytometric Annexin-V-PI and immunohistochemical (Ki-67, caspase 3, 8, 9) methods.Results:After free DOX and LipoDOX were applied, the proliferation index of three cell lines reduced. Intrinsic and extrinsic apoptotic pathways were activated in both 2D and 3D models. However, this effect was observed at lower levels in the 3D model due to the difficulty of diffusion of DOX into the spheroids. Additionally, the suitability of the 3D model for breast cancer cells was supported by formation of ductus-like structures and spheroids. Cell deaths were not observed significantly with the DOX-loaded microbubbles due to rising of MBs to the surface and not reaching spheroids held in matrigel of 3D model.Conclusion:DOX and LipoDOX showed anti-proliferative and apoptosis-inducing effects in breast cancer cells. However, these effects indicated variability depending on the cell lines and 2D or 3D model types. http://www.eurjbreasthealth.com/archives/archive-detail/article-preview/evaluation-of-liposomal-and-microbubbles-mediated-/47936 3d cell culturebreast cancerdoxorubicinliposomemicrobubble
spellingShingle Melek Aydın
Ekrem Özdemir
Zekiye Altun
Sevgi Kılıç
Safiye Aktaş
Evaluation of Liposomal and Microbubbles Mediated Delivery of Doxorubicin in Two-Dimensional (2D) and Three-Dimensional (3D) Models for Breast Cancer
European Journal of Breast Health
3d cell culture
breast cancer
doxorubicin
liposome
microbubble
title Evaluation of Liposomal and Microbubbles Mediated Delivery of Doxorubicin in Two-Dimensional (2D) and Three-Dimensional (3D) Models for Breast Cancer
title_full Evaluation of Liposomal and Microbubbles Mediated Delivery of Doxorubicin in Two-Dimensional (2D) and Three-Dimensional (3D) Models for Breast Cancer
title_fullStr Evaluation of Liposomal and Microbubbles Mediated Delivery of Doxorubicin in Two-Dimensional (2D) and Three-Dimensional (3D) Models for Breast Cancer
title_full_unstemmed Evaluation of Liposomal and Microbubbles Mediated Delivery of Doxorubicin in Two-Dimensional (2D) and Three-Dimensional (3D) Models for Breast Cancer
title_short Evaluation of Liposomal and Microbubbles Mediated Delivery of Doxorubicin in Two-Dimensional (2D) and Three-Dimensional (3D) Models for Breast Cancer
title_sort evaluation of liposomal and microbubbles mediated delivery of doxorubicin in two dimensional 2d and three dimensional 3d models for breast cancer
topic 3d cell culture
breast cancer
doxorubicin
liposome
microbubble
url http://www.eurjbreasthealth.com/archives/archive-detail/article-preview/evaluation-of-liposomal-and-microbubbles-mediated-/47936
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AT ekremozdemir evaluationofliposomalandmicrobubblesmediateddeliveryofdoxorubicinintwodimensional2dandthreedimensional3dmodelsforbreastcancer
AT zekiyealtun evaluationofliposomalandmicrobubblesmediateddeliveryofdoxorubicinintwodimensional2dandthreedimensional3dmodelsforbreastcancer
AT sevgikılıc evaluationofliposomalandmicrobubblesmediateddeliveryofdoxorubicinintwodimensional2dandthreedimensional3dmodelsforbreastcancer
AT safiyeaktas evaluationofliposomalandmicrobubblesmediateddeliveryofdoxorubicinintwodimensional2dandthreedimensional3dmodelsforbreastcancer