Magnetoliposomes with Calcium-Doped Magnesium Ferrites Anchored in the Lipid Surface for Enhanced DOX Release

Nanotechnology has provided a new insight into cancer treatment by enabling the development of nanocarriers for the encapsulation, transport, and controlled release of antitumor drugs at the target site. Among these nanocarriers, magnetic nanosystems have gained prominence. This work presents the de...

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Main Authors: Beatriz D. Cardoso, Diana E. M. Fernandes, Carlos O. Amorim, Vítor S. Amaral, Paulo J. G. Coutinho, Ana Rita O. Rodrigues, Elisabete M. S. Castanheira
Format: Article
Language:English
Published: MDPI AG 2023-09-01
Series:Nanomaterials
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Online Access:https://www.mdpi.com/2079-4991/13/18/2597
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author Beatriz D. Cardoso
Diana E. M. Fernandes
Carlos O. Amorim
Vítor S. Amaral
Paulo J. G. Coutinho
Ana Rita O. Rodrigues
Elisabete M. S. Castanheira
author_facet Beatriz D. Cardoso
Diana E. M. Fernandes
Carlos O. Amorim
Vítor S. Amaral
Paulo J. G. Coutinho
Ana Rita O. Rodrigues
Elisabete M. S. Castanheira
author_sort Beatriz D. Cardoso
collection DOAJ
description Nanotechnology has provided a new insight into cancer treatment by enabling the development of nanocarriers for the encapsulation, transport, and controlled release of antitumor drugs at the target site. Among these nanocarriers, magnetic nanosystems have gained prominence. This work presents the design, development, and characterization of magnetoliposomes (MLs), wherein superparamagnetic nanoparticles are coupled to the lipid surface. For this purpose, dimercaptosuccinic acid (DMSA)-functionalized Ca<sub>0.25</sub>Mg<sub>0.75</sub>Fe<sub>2</sub>O<sub>4</sub> superparamagnetic nanoparticles were prepared for the first time. The magnetic nanoparticles demonstrated a cubic shape with an average size of 13.36 nm. Furthermore, their potential for photothermal hyperthermia was evaluated using 4 mg/mL, 2 mg/mL, and 1 mg/mL concentrations of NPs@DMSA, which demonstrated a maximum temperature variation of 20.4 °C, 11.4 °C, and 7.3 °C, respectively, during a 30 min NIR-laser irradiation. Subsequently, these nanoparticles were coupled to the lipid surface of DPPC/DSPC/CHEMS and DPPC/DSPC/CHEMS/DSPE-PEG-based MLs using a new synthesis methodology, exhibiting average sizes of 153 ± 8 nm and 136 ± 2 nm, respectively. Doxorubicin (DOX) was encapsulated with high efficiency, achieving 96% ± 2% encapsulation in non-PEGylated MLs and 98.0% ± 0.6% in stealth MLs. Finally, drug release assays of the DOX-loaded DPPC/DSPC/CHEMS MLs were performed under different conditions of temperature (37 °C and 42 °C) and pH (5.5 and 7.4), simulating physiological and therapeutic conditions. The results revealed a higher release rate at 42 °C and acidic pH. Release rates significantly increased when introducing the stimulus of laser-induced photothermal hyperthermia at 808 nm (1 W/cm<sup>2</sup>) for 5 min. After 48 h of testing, at pH 5.5, 67.5% ± 0.5% of DOX was released, while at pH 7.4, only a modest release of 27.0% ± 0.1% was achieved. The results demonstrate the potential of the MLs developed in this work to the controlled release of DOX under NIR-laser stimulation and acidic environments and to maintain a sustained and reduced release profile in physiological environments with pH 7.4.
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spelling doaj.art-36fb58703da34c82856a4f025262f1fb2023-11-19T12:15:15ZengMDPI AGNanomaterials2079-49912023-09-011318259710.3390/nano13182597Magnetoliposomes with Calcium-Doped Magnesium Ferrites Anchored in the Lipid Surface for Enhanced DOX ReleaseBeatriz D. Cardoso0Diana E. M. Fernandes1Carlos O. Amorim2Vítor S. Amaral3Paulo J. G. Coutinho4Ana Rita O. Rodrigues5Elisabete M. S. Castanheira6Physics Centre of Minho and Porto Universities (CF-UM-UP), Campus de Gualtar, 4710-057 Braga, PortugalPhysics Centre of Minho and Porto Universities (CF-UM-UP), Campus de Gualtar, 4710-057 Braga, PortugalPhysics Department and CICECO, University of Aveiro, Campus de Santiago, 3810-193 Aveiro, PortugalPhysics Department and CICECO, University of Aveiro, Campus de Santiago, 3810-193 Aveiro, PortugalPhysics Centre of Minho and Porto Universities (CF-UM-UP), Campus de Gualtar, 4710-057 Braga, PortugalPhysics Centre of Minho and Porto Universities (CF-UM-UP), Campus de Gualtar, 4710-057 Braga, PortugalPhysics Centre of Minho and Porto Universities (CF-UM-UP), Campus de Gualtar, 4710-057 Braga, PortugalNanotechnology has provided a new insight into cancer treatment by enabling the development of nanocarriers for the encapsulation, transport, and controlled release of antitumor drugs at the target site. Among these nanocarriers, magnetic nanosystems have gained prominence. This work presents the design, development, and characterization of magnetoliposomes (MLs), wherein superparamagnetic nanoparticles are coupled to the lipid surface. For this purpose, dimercaptosuccinic acid (DMSA)-functionalized Ca<sub>0.25</sub>Mg<sub>0.75</sub>Fe<sub>2</sub>O<sub>4</sub> superparamagnetic nanoparticles were prepared for the first time. The magnetic nanoparticles demonstrated a cubic shape with an average size of 13.36 nm. Furthermore, their potential for photothermal hyperthermia was evaluated using 4 mg/mL, 2 mg/mL, and 1 mg/mL concentrations of NPs@DMSA, which demonstrated a maximum temperature variation of 20.4 °C, 11.4 °C, and 7.3 °C, respectively, during a 30 min NIR-laser irradiation. Subsequently, these nanoparticles were coupled to the lipid surface of DPPC/DSPC/CHEMS and DPPC/DSPC/CHEMS/DSPE-PEG-based MLs using a new synthesis methodology, exhibiting average sizes of 153 ± 8 nm and 136 ± 2 nm, respectively. Doxorubicin (DOX) was encapsulated with high efficiency, achieving 96% ± 2% encapsulation in non-PEGylated MLs and 98.0% ± 0.6% in stealth MLs. Finally, drug release assays of the DOX-loaded DPPC/DSPC/CHEMS MLs were performed under different conditions of temperature (37 °C and 42 °C) and pH (5.5 and 7.4), simulating physiological and therapeutic conditions. The results revealed a higher release rate at 42 °C and acidic pH. Release rates significantly increased when introducing the stimulus of laser-induced photothermal hyperthermia at 808 nm (1 W/cm<sup>2</sup>) for 5 min. After 48 h of testing, at pH 5.5, 67.5% ± 0.5% of DOX was released, while at pH 7.4, only a modest release of 27.0% ± 0.1% was achieved. The results demonstrate the potential of the MLs developed in this work to the controlled release of DOX under NIR-laser stimulation and acidic environments and to maintain a sustained and reduced release profile in physiological environments with pH 7.4.https://www.mdpi.com/2079-4991/13/18/2597stimuli-responsive magnetoliposomesmagnetic nanoparticlescubic shapedoxorubicinhyperthermiacontrolled drug release
spellingShingle Beatriz D. Cardoso
Diana E. M. Fernandes
Carlos O. Amorim
Vítor S. Amaral
Paulo J. G. Coutinho
Ana Rita O. Rodrigues
Elisabete M. S. Castanheira
Magnetoliposomes with Calcium-Doped Magnesium Ferrites Anchored in the Lipid Surface for Enhanced DOX Release
Nanomaterials
stimuli-responsive magnetoliposomes
magnetic nanoparticles
cubic shape
doxorubicin
hyperthermia
controlled drug release
title Magnetoliposomes with Calcium-Doped Magnesium Ferrites Anchored in the Lipid Surface for Enhanced DOX Release
title_full Magnetoliposomes with Calcium-Doped Magnesium Ferrites Anchored in the Lipid Surface for Enhanced DOX Release
title_fullStr Magnetoliposomes with Calcium-Doped Magnesium Ferrites Anchored in the Lipid Surface for Enhanced DOX Release
title_full_unstemmed Magnetoliposomes with Calcium-Doped Magnesium Ferrites Anchored in the Lipid Surface for Enhanced DOX Release
title_short Magnetoliposomes with Calcium-Doped Magnesium Ferrites Anchored in the Lipid Surface for Enhanced DOX Release
title_sort magnetoliposomes with calcium doped magnesium ferrites anchored in the lipid surface for enhanced dox release
topic stimuli-responsive magnetoliposomes
magnetic nanoparticles
cubic shape
doxorubicin
hyperthermia
controlled drug release
url https://www.mdpi.com/2079-4991/13/18/2597
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