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Biocompatibility and cytotoxicity in vitro of surface-functionalized drug-loaded spinel ferrite nanoparticles

In this study, poly(isobutylene-alt-maleic anhydride) (PMA)-coated spinel ferrite (MFe(2)O(4), where M = Fe, Co, Ni, or Zn) nanoparticles (NPs) were developed as carriers of the anticancer drugs doxorubicin (DOX) and methotrexate (MTX). Physical characterizations confirmed the formation of pure cubi...

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Autores principales: Mushtaq, Sadaf, Shahzad, Khuram, Saeed, Tariq, Ul-Hamid, Anwar, Abbasi, Bilal Haider, Ahmad, Nafees, Khalid, Waqas, Atif, Muhammad, Ali, Zulqurnain, Abbasi, Rashda
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Beilstein-Institut 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8649206/
https://www.ncbi.nlm.nih.gov/pubmed/34934608
http://dx.doi.org/10.3762/bjnano.12.99
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author Mushtaq, Sadaf
Shahzad, Khuram
Saeed, Tariq
Ul-Hamid, Anwar
Abbasi, Bilal Haider
Ahmad, Nafees
Khalid, Waqas
Atif, Muhammad
Ali, Zulqurnain
Abbasi, Rashda
author_facet Mushtaq, Sadaf
Shahzad, Khuram
Saeed, Tariq
Ul-Hamid, Anwar
Abbasi, Bilal Haider
Ahmad, Nafees
Khalid, Waqas
Atif, Muhammad
Ali, Zulqurnain
Abbasi, Rashda
author_sort Mushtaq, Sadaf
collection PubMed
description In this study, poly(isobutylene-alt-maleic anhydride) (PMA)-coated spinel ferrite (MFe(2)O(4), where M = Fe, Co, Ni, or Zn) nanoparticles (NPs) were developed as carriers of the anticancer drugs doxorubicin (DOX) and methotrexate (MTX). Physical characterizations confirmed the formation of pure cubic structures (14–22 nm) with magnetic properties. Drug-loaded NPs exhibited tumor specificity with significantly higher (p < 0.005) drug release in an acidic environment (pH 5.5). The nanoparticles were highly colloidal (zeta potential = −35 to −26 mV) in deionized water, phosphate buffer saline (PBS), and sodium borate buffer (SBB). They showed elevated and dose-dependent cytotoxicity in vitro compared to free drug controls. The IC(50) values ranged from 0.81 to 3.97 μg/mL for HepG2 and HT144 cells, whereas IC(50) values for normal lymphocytes were 10 to 35 times higher (18.35–43.04 µg/mL). Cobalt ferrite (CFO) and zinc ferrite (ZFO) NPs were highly genotoxic (p < 0.05) in cancer cell lines. The nanoparticles caused cytotoxicity via oxidative stress, causing DNA damage and activation of p53-mediated cell cycle arrest (significantly elevated expression, p < 0.005, majorly G1 and G2/M arrest) and apoptosis. Cytotoxicity testing in 3D spheroids showed significant (p < 0.05) reduction in spheroid diameter and up to 74 ± 8.9% of cell death after two weeks. In addition, they also inhibited multidrug resistance (MDR) pump activity in both cell lines suggesting effectivity in MDR cancers. Among the tested MFe(2)O(4) NPs, CFO nanocarriers were the most favorable for targeted cancer therapy due to excellent magnetic, colloidal, cytotoxic, and biocompatible aspects. However, detailed mechanistic, in vivo cytotoxicity, and magnetic-field-assisted studies are required to fully exploit these nanocarriers in therapeutic applications.
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spelling pubmed-86492062021-12-20 Biocompatibility and cytotoxicity in vitro of surface-functionalized drug-loaded spinel ferrite nanoparticles Mushtaq, Sadaf Shahzad, Khuram Saeed, Tariq Ul-Hamid, Anwar Abbasi, Bilal Haider Ahmad, Nafees Khalid, Waqas Atif, Muhammad Ali, Zulqurnain Abbasi, Rashda Beilstein J Nanotechnol Full Research Paper In this study, poly(isobutylene-alt-maleic anhydride) (PMA)-coated spinel ferrite (MFe(2)O(4), where M = Fe, Co, Ni, or Zn) nanoparticles (NPs) were developed as carriers of the anticancer drugs doxorubicin (DOX) and methotrexate (MTX). Physical characterizations confirmed the formation of pure cubic structures (14–22 nm) with magnetic properties. Drug-loaded NPs exhibited tumor specificity with significantly higher (p < 0.005) drug release in an acidic environment (pH 5.5). The nanoparticles were highly colloidal (zeta potential = −35 to −26 mV) in deionized water, phosphate buffer saline (PBS), and sodium borate buffer (SBB). They showed elevated and dose-dependent cytotoxicity in vitro compared to free drug controls. The IC(50) values ranged from 0.81 to 3.97 μg/mL for HepG2 and HT144 cells, whereas IC(50) values for normal lymphocytes were 10 to 35 times higher (18.35–43.04 µg/mL). Cobalt ferrite (CFO) and zinc ferrite (ZFO) NPs were highly genotoxic (p < 0.05) in cancer cell lines. The nanoparticles caused cytotoxicity via oxidative stress, causing DNA damage and activation of p53-mediated cell cycle arrest (significantly elevated expression, p < 0.005, majorly G1 and G2/M arrest) and apoptosis. Cytotoxicity testing in 3D spheroids showed significant (p < 0.05) reduction in spheroid diameter and up to 74 ± 8.9% of cell death after two weeks. In addition, they also inhibited multidrug resistance (MDR) pump activity in both cell lines suggesting effectivity in MDR cancers. Among the tested MFe(2)O(4) NPs, CFO nanocarriers were the most favorable for targeted cancer therapy due to excellent magnetic, colloidal, cytotoxic, and biocompatible aspects. However, detailed mechanistic, in vivo cytotoxicity, and magnetic-field-assisted studies are required to fully exploit these nanocarriers in therapeutic applications. Beilstein-Institut 2021-12-02 /pmc/articles/PMC8649206/ /pubmed/34934608 http://dx.doi.org/10.3762/bjnano.12.99 Text en Copyright © 2021, Mushtaq et al. https://creativecommons.org/licenses/by/4.0/This is an open access article licensed under the terms of the Beilstein-Institut Open Access License Agreement (https://www.beilstein-journals.org/bjnano/terms/terms), which is identical to the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0 (https://creativecommons.org/licenses/by/4.0/) ). The reuse of material under this license requires that the author(s), source and license are credited. Third-party material in this article could be subject to other licenses (typically indicated in the credit line), and in this case, users are required to obtain permission from the license holder to reuse the material.
spellingShingle Full Research Paper
Mushtaq, Sadaf
Shahzad, Khuram
Saeed, Tariq
Ul-Hamid, Anwar
Abbasi, Bilal Haider
Ahmad, Nafees
Khalid, Waqas
Atif, Muhammad
Ali, Zulqurnain
Abbasi, Rashda
Biocompatibility and cytotoxicity in vitro of surface-functionalized drug-loaded spinel ferrite nanoparticles
title Biocompatibility and cytotoxicity in vitro of surface-functionalized drug-loaded spinel ferrite nanoparticles
title_full Biocompatibility and cytotoxicity in vitro of surface-functionalized drug-loaded spinel ferrite nanoparticles
title_fullStr Biocompatibility and cytotoxicity in vitro of surface-functionalized drug-loaded spinel ferrite nanoparticles
title_full_unstemmed Biocompatibility and cytotoxicity in vitro of surface-functionalized drug-loaded spinel ferrite nanoparticles
title_short Biocompatibility and cytotoxicity in vitro of surface-functionalized drug-loaded spinel ferrite nanoparticles
title_sort biocompatibility and cytotoxicity in vitro of surface-functionalized drug-loaded spinel ferrite nanoparticles
topic Full Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8649206/
https://www.ncbi.nlm.nih.gov/pubmed/34934608
http://dx.doi.org/10.3762/bjnano.12.99
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