LDL-Based Lipid Nanoparticle Derived for Blood Plasma Accumulates Preferentially in Atherosclerotic Plaque

Apolipoprotein-based drug delivery is a promising approach to develop safe nanoparticles capable of targeted drug delivery for various diseases. In this work, we have synthesized a lipid-based nanoparticle (NPs) that we have called “Aposomes” presenting native apolipoprotein B-100 (apoB-100), the pr...

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Autores principales:	Christian A. Boada, Assaf Zinger, Scott Rohen, Jonathan O. Martinez, Michael Evangelopoulos, Roberto Molinaro, Madeleine Lu, Ramiro Alejandro Villarreal-Leal, Federica Giordano, Manuela Sushnitha, Enrica De Rosa, Jens B. Simonsen, Sergey Shevkoplyas, Francesca Taraballi, Ennio Tasciotti
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	LDL Apolipoprotein Rapamycin Liposome Nanoparticle Drug Delivery Biotechnology TP248.13-248.65
Acceso en línea:	https://doaj.org/article/1431445ef19540ffbdf36c33e227fd00
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spelling	oai:doaj.org-article:1431445ef19540ffbdf36c33e227fd002021-12-02T00:12:34ZLDL-Based Lipid Nanoparticle Derived for Blood Plasma Accumulates Preferentially in Atherosclerotic Plaque2296-418510.3389/fbioe.2021.794676https://doaj.org/article/1431445ef19540ffbdf36c33e227fd002021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fbioe.2021.794676/fullhttps://doaj.org/toc/2296-4185Apolipoprotein-based drug delivery is a promising approach to develop safe nanoparticles capable of targeted drug delivery for various diseases. In this work, we have synthesized a lipid-based nanoparticle (NPs) that we have called “Aposomes” presenting native apolipoprotein B-100 (apoB-100), the primary protein present in Low-Density Lipoproteins (LDL) on its surface. The aposomes were synthesized from LDL isolated from blood plasma using a microfluidic approach. The synthesized aposomes had a diameter of 91 ± 4 nm and a neutral surface charge of 0.7 mV ± mV. Protein analysis using western blot and flow cytometry confirmed the presence of apoB-100 on the nanoparticle’s surface. Furthermore, Aposomes retained liposomes’ drug loading capabilities, demonstrating a prolonged release curve with ∼80% cargo release at 4 hours. Considering the natural tropism of LDL towards the atherosclerotic plaques, we evaluated the biological properties of aposomes in a mouse model of advanced atherosclerosis. We observed a ∼20-fold increase in targeting of plaques when comparing aposomes to control liposomes. Additionally, aposomes presented a favorable biocompatibility profile that showed no deviation from typical values in liver toxicity markers (i.e., LDH, ALT, AST, Cholesterol). The results of this study demonstrate the possibilities of using apolipoprotein-based approaches to create nanoparticles with active targeting capabilities and could be the basis for future cardiovascular therapies.Christian A. BoadaChristian A. BoadaAssaf ZingerAssaf ZingerAssaf ZingerScott RohenJonathan O. MartinezMichael EvangelopoulosRoberto MolinaroRoberto MolinaroMadeleine LuRamiro Alejandro Villarreal-LealRamiro Alejandro Villarreal-LealFederica GiordanoFederica GiordanoManuela SushnithaEnrica De RosaJens B. SimonsenSergey ShevkoplyasFrancesca TaraballiFrancesca TaraballiEnnio TasciottiFrontiers Media S.A.articleLDLApolipoproteinRapamycinLiposomeNanoparticleDrug DeliveryBiotechnologyTP248.13-248.65ENFrontiers in Bioengineering and Biotechnology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	LDL Apolipoprotein Rapamycin Liposome Nanoparticle Drug Delivery Biotechnology TP248.13-248.65
spellingShingle	LDL Apolipoprotein Rapamycin Liposome Nanoparticle Drug Delivery Biotechnology TP248.13-248.65 Christian A. Boada Christian A. Boada Assaf Zinger Assaf Zinger Assaf Zinger Scott Rohen Jonathan O. Martinez Michael Evangelopoulos Roberto Molinaro Roberto Molinaro Madeleine Lu Ramiro Alejandro Villarreal-Leal Ramiro Alejandro Villarreal-Leal Federica Giordano Federica Giordano Manuela Sushnitha Enrica De Rosa Jens B. Simonsen Sergey Shevkoplyas Francesca Taraballi Francesca Taraballi Ennio Tasciotti LDL-Based Lipid Nanoparticle Derived for Blood Plasma Accumulates Preferentially in Atherosclerotic Plaque
description	Apolipoprotein-based drug delivery is a promising approach to develop safe nanoparticles capable of targeted drug delivery for various diseases. In this work, we have synthesized a lipid-based nanoparticle (NPs) that we have called “Aposomes” presenting native apolipoprotein B-100 (apoB-100), the primary protein present in Low-Density Lipoproteins (LDL) on its surface. The aposomes were synthesized from LDL isolated from blood plasma using a microfluidic approach. The synthesized aposomes had a diameter of 91 ± 4 nm and a neutral surface charge of 0.7 mV ± mV. Protein analysis using western blot and flow cytometry confirmed the presence of apoB-100 on the nanoparticle’s surface. Furthermore, Aposomes retained liposomes’ drug loading capabilities, demonstrating a prolonged release curve with ∼80% cargo release at 4 hours. Considering the natural tropism of LDL towards the atherosclerotic plaques, we evaluated the biological properties of aposomes in a mouse model of advanced atherosclerosis. We observed a ∼20-fold increase in targeting of plaques when comparing aposomes to control liposomes. Additionally, aposomes presented a favorable biocompatibility profile that showed no deviation from typical values in liver toxicity markers (i.e., LDH, ALT, AST, Cholesterol). The results of this study demonstrate the possibilities of using apolipoprotein-based approaches to create nanoparticles with active targeting capabilities and could be the basis for future cardiovascular therapies.
format	article
author	Christian A. Boada Christian A. Boada Assaf Zinger Assaf Zinger Assaf Zinger Scott Rohen Jonathan O. Martinez Michael Evangelopoulos Roberto Molinaro Roberto Molinaro Madeleine Lu Ramiro Alejandro Villarreal-Leal Ramiro Alejandro Villarreal-Leal Federica Giordano Federica Giordano Manuela Sushnitha Enrica De Rosa Jens B. Simonsen Sergey Shevkoplyas Francesca Taraballi Francesca Taraballi Ennio Tasciotti
author_facet	Christian A. Boada Christian A. Boada Assaf Zinger Assaf Zinger Assaf Zinger Scott Rohen Jonathan O. Martinez Michael Evangelopoulos Roberto Molinaro Roberto Molinaro Madeleine Lu Ramiro Alejandro Villarreal-Leal Ramiro Alejandro Villarreal-Leal Federica Giordano Federica Giordano Manuela Sushnitha Enrica De Rosa Jens B. Simonsen Sergey Shevkoplyas Francesca Taraballi Francesca Taraballi Ennio Tasciotti
author_sort	Christian A. Boada
title	LDL-Based Lipid Nanoparticle Derived for Blood Plasma Accumulates Preferentially in Atherosclerotic Plaque
title_short	LDL-Based Lipid Nanoparticle Derived for Blood Plasma Accumulates Preferentially in Atherosclerotic Plaque
title_full	LDL-Based Lipid Nanoparticle Derived for Blood Plasma Accumulates Preferentially in Atherosclerotic Plaque
title_fullStr	LDL-Based Lipid Nanoparticle Derived for Blood Plasma Accumulates Preferentially in Atherosclerotic Plaque
title_full_unstemmed	LDL-Based Lipid Nanoparticle Derived for Blood Plasma Accumulates Preferentially in Atherosclerotic Plaque
title_sort	ldl-based lipid nanoparticle derived for blood plasma accumulates preferentially in atherosclerotic plaque
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/1431445ef19540ffbdf36c33e227fd00
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LDL-Based Lipid Nanoparticle Derived for Blood Plasma Accumulates Preferentially in Atherosclerotic Plaque

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