Impact of atorvastatin loaded exosome as an anti-glioblastoma carrier to induce apoptosis of U87 cancer cells in 3D culture model

Exosomes (EXOs) are naturally occurring nanosized lipid bilayers that can be efficiently used as a drug delivery system to carry small pharmaceutical, biological molecules and pass major biological barriers such as the blood-brain barrier. It was hypothesized that EXOs derived from human endometrial...

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Main Authors: Vajihe Taghdiri Nooshabadi, Mehdi Khanmohammadi, Shilan Shafei, Hamid Reza Banafshe, Ziba Veisi Malekshahi, Somayeh Ebrahimi-Barough, Jafar Ai
Format: Article
Language:English
Published: Elsevier 2020-09-01
Series:Biochemistry and Biophysics Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2405580820301011
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author Vajihe Taghdiri Nooshabadi
Mehdi Khanmohammadi
Shilan Shafei
Hamid Reza Banafshe
Ziba Veisi Malekshahi
Somayeh Ebrahimi-Barough
Jafar Ai
author_facet Vajihe Taghdiri Nooshabadi
Mehdi Khanmohammadi
Shilan Shafei
Hamid Reza Banafshe
Ziba Veisi Malekshahi
Somayeh Ebrahimi-Barough
Jafar Ai
author_sort Vajihe Taghdiri Nooshabadi
collection DOAJ
description Exosomes (EXOs) are naturally occurring nanosized lipid bilayers that can be efficiently used as a drug delivery system to carry small pharmaceutical, biological molecules and pass major biological barriers such as the blood-brain barrier. It was hypothesized that EXOs derived from human endometrial stem cells (hEnSCs-EXOs) can be utilized as a drug carrier to enhance tumor-targeting drugs, especially for those have low solubility and limited oral bioactivity. In this study, atorvastatin (Ato) loaded EXOs (AtoEXOs) was prepared and characterized for its physical and biological activities in tumor growth suppression of 3 D glioblastoma model. The AtoEXOs were obtained in different methods to maximize drug encapsulation efficacy. The characterization of AtoEXOs was performed for its size, stability, drug release, and in vitro anti-tumor efficacy evaluated comprising inhibition of proliferation, apoptosis induction of tumor cells. Expression of apoptotic genes by Real time PCR, Annexin V/PI, tunnel assay was studied after 72 h exposing U87 cells where encapsulated in matrigel in different concentrations of AtoEXOs (5, 10 μM). The results showed that the prepared AtoEXOs possessed diameter ranging from 30–150 nm, satisfying stability and sustainable Ato release rate. The AtoEXOs was up taken by U87 and generated significant apoptotic effects while this inhibited tumor growth of U87 cells. Altogether, produced AtoEXOs formulation due to its therapeutic efficacy has the potential to be an adaptable approach to treat glioblastoma brain tumors.
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spelling doaj.art-1100bbd882ce4ac9886c6b8cb91e81332022-12-21T23:43:25ZengElsevierBiochemistry and Biophysics Reports2405-58082020-09-0123100792Impact of atorvastatin loaded exosome as an anti-glioblastoma carrier to induce apoptosis of U87 cancer cells in 3D culture modelVajihe Taghdiri Nooshabadi0Mehdi Khanmohammadi1Shilan Shafei2Hamid Reza Banafshe3Ziba Veisi Malekshahi4Somayeh Ebrahimi-Barough5Jafar Ai6Department of Tissue Engineering and Applied Cell Sciences, School of Medicine, Semnan University of Medical Science, Semnan, Iran; Department of Applied Cell Sciences, Kashan University of Medical Sciences, Kashan, IranSkull Based Research Center and Department, The Five Senses Institute, Hazrat Rasoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran; Corresponding author.Department of Molecular Medicine, School of Advanced Technologies in Medicine, International Campus Tehran University of Medical Sciences, Tehran, IranDepartment of Applied Cell Sciences, Kashan University of Medical Sciences, Kashan, IranDepartment of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran, University of Medical Sciences, Tehran, IranDepartment of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, 1417743361, IranDepartment of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, 1417743361, Iran; Corresponding author.Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.Exosomes (EXOs) are naturally occurring nanosized lipid bilayers that can be efficiently used as a drug delivery system to carry small pharmaceutical, biological molecules and pass major biological barriers such as the blood-brain barrier. It was hypothesized that EXOs derived from human endometrial stem cells (hEnSCs-EXOs) can be utilized as a drug carrier to enhance tumor-targeting drugs, especially for those have low solubility and limited oral bioactivity. In this study, atorvastatin (Ato) loaded EXOs (AtoEXOs) was prepared and characterized for its physical and biological activities in tumor growth suppression of 3 D glioblastoma model. The AtoEXOs were obtained in different methods to maximize drug encapsulation efficacy. The characterization of AtoEXOs was performed for its size, stability, drug release, and in vitro anti-tumor efficacy evaluated comprising inhibition of proliferation, apoptosis induction of tumor cells. Expression of apoptotic genes by Real time PCR, Annexin V/PI, tunnel assay was studied after 72 h exposing U87 cells where encapsulated in matrigel in different concentrations of AtoEXOs (5, 10 μM). The results showed that the prepared AtoEXOs possessed diameter ranging from 30–150 nm, satisfying stability and sustainable Ato release rate. The AtoEXOs was up taken by U87 and generated significant apoptotic effects while this inhibited tumor growth of U87 cells. Altogether, produced AtoEXOs formulation due to its therapeutic efficacy has the potential to be an adaptable approach to treat glioblastoma brain tumors.http://www.sciencedirect.com/science/article/pii/S2405580820301011Atorvastatin loaded exosomeGlioblastomaApoptotic effectsanti-Glioblastoma carrier
spellingShingle Vajihe Taghdiri Nooshabadi
Mehdi Khanmohammadi
Shilan Shafei
Hamid Reza Banafshe
Ziba Veisi Malekshahi
Somayeh Ebrahimi-Barough
Jafar Ai
Impact of atorvastatin loaded exosome as an anti-glioblastoma carrier to induce apoptosis of U87 cancer cells in 3D culture model
Biochemistry and Biophysics Reports
Atorvastatin loaded exosome
Glioblastoma
Apoptotic effects
anti-Glioblastoma carrier
title Impact of atorvastatin loaded exosome as an anti-glioblastoma carrier to induce apoptosis of U87 cancer cells in 3D culture model
title_full Impact of atorvastatin loaded exosome as an anti-glioblastoma carrier to induce apoptosis of U87 cancer cells in 3D culture model
title_fullStr Impact of atorvastatin loaded exosome as an anti-glioblastoma carrier to induce apoptosis of U87 cancer cells in 3D culture model
title_full_unstemmed Impact of atorvastatin loaded exosome as an anti-glioblastoma carrier to induce apoptosis of U87 cancer cells in 3D culture model
title_short Impact of atorvastatin loaded exosome as an anti-glioblastoma carrier to induce apoptosis of U87 cancer cells in 3D culture model
title_sort impact of atorvastatin loaded exosome as an anti glioblastoma carrier to induce apoptosis of u87 cancer cells in 3d culture model
topic Atorvastatin loaded exosome
Glioblastoma
Apoptotic effects
anti-Glioblastoma carrier
url http://www.sciencedirect.com/science/article/pii/S2405580820301011
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