Engineered hyaluronic acid-decorated niosomal nanoparticles for controlled and targeted delivery of epirubicin to treat breast cancer

Targeted drug delivery systems using nanocarriers offer a versatile platform for breast cancer treatment; however, a robust, CD44-targeted niosomal formulation has not been developed and deeply studied (both in vitro and in vivo) yet. Here, an optimized system of epirubicin (Epi)-loaded niosomal nan...

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Main Authors: Amirreza Mansoori-Kermani, Sadaf Khalighi, Iman Akbarzadeh, Fazeleh Ranjbar Niavol, Hamidreza Motasadizadeh, Athar Mahdieh, Vahid Jahed, Masoud Abdinezhad, Nikoo Rahbariasr, Mahshid Hosseini, Nima Ahmadkhani, Behnam Panahi, Yousef Fatahi, Masoud Mozafari, Alan Prem Kumar, Ebrahim Mostafavi
Format: Article
Language:English
Published: Elsevier 2022-12-01
Series:Materials Today Bio
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2590006422001478
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author Amirreza Mansoori-Kermani
Sadaf Khalighi
Iman Akbarzadeh
Fazeleh Ranjbar Niavol
Hamidreza Motasadizadeh
Athar Mahdieh
Vahid Jahed
Masoud Abdinezhad
Nikoo Rahbariasr
Mahshid Hosseini
Nima Ahmadkhani
Behnam Panahi
Yousef Fatahi
Masoud Mozafari
Alan Prem Kumar
Ebrahim Mostafavi
author_facet Amirreza Mansoori-Kermani
Sadaf Khalighi
Iman Akbarzadeh
Fazeleh Ranjbar Niavol
Hamidreza Motasadizadeh
Athar Mahdieh
Vahid Jahed
Masoud Abdinezhad
Nikoo Rahbariasr
Mahshid Hosseini
Nima Ahmadkhani
Behnam Panahi
Yousef Fatahi
Masoud Mozafari
Alan Prem Kumar
Ebrahim Mostafavi
author_sort Amirreza Mansoori-Kermani
collection DOAJ
description Targeted drug delivery systems using nanocarriers offer a versatile platform for breast cancer treatment; however, a robust, CD44-targeted niosomal formulation has not been developed and deeply studied (both in vitro and in vivo) yet. Here, an optimized system of epirubicin (Epi)-loaded niosomal nanoparticles (Nio) coated with hyaluronic acid (HA) has been engineered for targeting breast cancer cells. The nanoformulation was first optimized (based on size, polydispersity index, and entrapment efficiency); then, we characterized the morphology, stability, and release behavior of the nanoparticles. Epirubicin release from the HA-coated system (Epi-Nio-HA) showed a 21% (acidic buffer) and 20% (neutral buffer) reduction in comparison with the non-coated group (Epi-Nio). The cytotoxicity and apoptosis results of 4T1 and SkBr3 cells showed an approximately 2-fold increase in the Epi-Nio-HA system over Epi-Nio and free epirubicin, which confirms the superiority of the engineered nanocarriers. Moreover, real-time PCR data demonstrated the down-regulation of the MMP-2, MMP-9, cyclin D, and cyclin E genes expression while caspase-3 and caspase-9 gene expression were up-regulated. Confocal microscopy and flow cytometry studies uncovered the cellular uptake mechanism of the Epi-Nio-HA system, which was CD44-mediated. Furthermore, in vivo studies indicated Epi-Nio-HA decreased mice breast tumor volume by 28% (compared to epirubicin) without side effects on the liver and kidney. Conclusively, our results indicated that the HA-functionalized niosomes provide a promising nanoplatform for efficient and targeted delivery of epirubicin to potentially treat breast cancer.
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spelling doaj.art-02cfa869d1c74127ba9aeba18bfe202f2022-12-22T03:34:01ZengElsevierMaterials Today Bio2590-00642022-12-0116100349Engineered hyaluronic acid-decorated niosomal nanoparticles for controlled and targeted delivery of epirubicin to treat breast cancerAmirreza Mansoori-Kermani0Sadaf Khalighi1Iman Akbarzadeh2Fazeleh Ranjbar Niavol3Hamidreza Motasadizadeh4Athar Mahdieh5Vahid Jahed6Masoud Abdinezhad7Nikoo Rahbariasr8Mahshid Hosseini9Nima Ahmadkhani10Behnam Panahi11Yousef Fatahi12Masoud Mozafari13Alan Prem Kumar14Ebrahim Mostafavi15Department of Chemical and Petrochemical Engineering, Sharif University of Technology, Tehran, IranDepartment of Chemical and Petrochemical Engineering, Sharif University of Technology, Tehran, IranDepartment of Chemical and Petrochemical Engineering, Sharif University of Technology, Tehran, IranDepartment of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, IranDepartment of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, IranDepartment of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, IranRudolfs Cimdins Riga Biomaterials Innovations and Development Centre of RTU, Institute of General Chemical Engineering, Faculty of Materials Science and Applied Chemistry, Riga Technical University, Pulka St. 3/3, Riga, LV, 1007, LatviaSchool of Chemical Engineering, College of Engineering, University of Tehran, Tehran, IranPolymer Research Laboratory, Department of Chemistry, Sharif University of Technology, Tehran, IranDepartment of Chemical and Petrochemical Engineering, Sharif University of Technology, Tehran, IranDepartment of Chemical and Petrochemical Engineering, Sharif University of Technology, Tehran, IranDepartment of Chemical and Petrochemical Engineering, Sharif University of Technology, Tehran, IranDepartment of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Nanotechnology Research Centre, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, IranDepartment of Tissue Engineering and Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran; Corresponding author. Currently at: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore; NUS Center for Cancer Research, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597, Singapore; Corresponding author. Cancer Science Institute of Singapore and Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117599, Singapore.Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, 94305, USA; Department of Medicine, Stanford University School of Medicine, Stanford, CA, 94305, USA; Corresponding author. Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA.Targeted drug delivery systems using nanocarriers offer a versatile platform for breast cancer treatment; however, a robust, CD44-targeted niosomal formulation has not been developed and deeply studied (both in vitro and in vivo) yet. Here, an optimized system of epirubicin (Epi)-loaded niosomal nanoparticles (Nio) coated with hyaluronic acid (HA) has been engineered for targeting breast cancer cells. The nanoformulation was first optimized (based on size, polydispersity index, and entrapment efficiency); then, we characterized the morphology, stability, and release behavior of the nanoparticles. Epirubicin release from the HA-coated system (Epi-Nio-HA) showed a 21% (acidic buffer) and 20% (neutral buffer) reduction in comparison with the non-coated group (Epi-Nio). The cytotoxicity and apoptosis results of 4T1 and SkBr3 cells showed an approximately 2-fold increase in the Epi-Nio-HA system over Epi-Nio and free epirubicin, which confirms the superiority of the engineered nanocarriers. Moreover, real-time PCR data demonstrated the down-regulation of the MMP-2, MMP-9, cyclin D, and cyclin E genes expression while caspase-3 and caspase-9 gene expression were up-regulated. Confocal microscopy and flow cytometry studies uncovered the cellular uptake mechanism of the Epi-Nio-HA system, which was CD44-mediated. Furthermore, in vivo studies indicated Epi-Nio-HA decreased mice breast tumor volume by 28% (compared to epirubicin) without side effects on the liver and kidney. Conclusively, our results indicated that the HA-functionalized niosomes provide a promising nanoplatform for efficient and targeted delivery of epirubicin to potentially treat breast cancer.http://www.sciencedirect.com/science/article/pii/S2590006422001478NanomedicineCD44Active targetingBreast cancerHyaluronic acidControlled drug delivery
spellingShingle Amirreza Mansoori-Kermani
Sadaf Khalighi
Iman Akbarzadeh
Fazeleh Ranjbar Niavol
Hamidreza Motasadizadeh
Athar Mahdieh
Vahid Jahed
Masoud Abdinezhad
Nikoo Rahbariasr
Mahshid Hosseini
Nima Ahmadkhani
Behnam Panahi
Yousef Fatahi
Masoud Mozafari
Alan Prem Kumar
Ebrahim Mostafavi
Engineered hyaluronic acid-decorated niosomal nanoparticles for controlled and targeted delivery of epirubicin to treat breast cancer
Materials Today Bio
Nanomedicine
CD44
Active targeting
Breast cancer
Hyaluronic acid
Controlled drug delivery
title Engineered hyaluronic acid-decorated niosomal nanoparticles for controlled and targeted delivery of epirubicin to treat breast cancer
title_full Engineered hyaluronic acid-decorated niosomal nanoparticles for controlled and targeted delivery of epirubicin to treat breast cancer
title_fullStr Engineered hyaluronic acid-decorated niosomal nanoparticles for controlled and targeted delivery of epirubicin to treat breast cancer
title_full_unstemmed Engineered hyaluronic acid-decorated niosomal nanoparticles for controlled and targeted delivery of epirubicin to treat breast cancer
title_short Engineered hyaluronic acid-decorated niosomal nanoparticles for controlled and targeted delivery of epirubicin to treat breast cancer
title_sort engineered hyaluronic acid decorated niosomal nanoparticles for controlled and targeted delivery of epirubicin to treat breast cancer
topic Nanomedicine
CD44
Active targeting
Breast cancer
Hyaluronic acid
Controlled drug delivery
url http://www.sciencedirect.com/science/article/pii/S2590006422001478
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