Controlled Functionalization Strategy of Proteins Preserves their Structural Integrity While Binding to Nanocarriers

Abstract The use of proteins as targeting agents often requires their chemical modification for their efficient attachment to a given surface. However, no control over the protein integrity and functionality has been demonstrated to date. Chemical over‐modification causes the loss of the native stru...

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Main Authors: Ana Mateos‐Maroto, Meiyu Gai, Maximilian Brückner, Volker Mailänder, Svenja Morsbach, Katharina Landfester
Format: Article
Language:English
Published: Wiley-VCH 2024-10-01
Series:Advanced Materials Interfaces
Subjects:
Online Access:https://doi.org/10.1002/admi.202400472
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author Ana Mateos‐Maroto
Meiyu Gai
Maximilian Brückner
Volker Mailänder
Svenja Morsbach
Katharina Landfester
author_facet Ana Mateos‐Maroto
Meiyu Gai
Maximilian Brückner
Volker Mailänder
Svenja Morsbach
Katharina Landfester
author_sort Ana Mateos‐Maroto
collection DOAJ
description Abstract The use of proteins as targeting agents often requires their chemical modification for their efficient attachment to a given surface. However, no control over the protein integrity and functionality has been demonstrated to date. Chemical over‐modification causes the loss of the native structure of the protein and thus limits its targeting efficiency. To preserve structural integrity, a minimal modification strategy of proteins is developed while maintaining their functionality. Apolipoprotein A1 (ApoA1) and liposomes are utilized as a nanocarrier platform. Monitoring NHS ester chemistry by time‐of‐flight mass spectrometry experiments, the proposed functionalization route allows the effective chemical coupling of the minimally modified ApoA1 to the surface of the liposomes via a click chemistry reaction. The stability of the modified ApoA1 is ensured by analyzing the secondary structure by circular dichroism spectroscopy and the corresponding melting point by nano differential scanning fluorimetry. Furthermore, ApoA1 attachment to the liposomes is confirmed by flow cytometry experiments. The procedure presented in this study has the potential to be easily transferred to other proteins while introducing only minimally necessary chemical modifications to be covalently attached to different drug delivery platforms. This can help to improve their targeting efficiency for future biomedical applications.
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institution OA Journals
issn 2196-7350
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publishDate 2024-10-01
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series Advanced Materials Interfaces
spelling doaj-art-2bac7266765d4f338945a37834bc033f2025-08-20T01:54:16ZengWiley-VCHAdvanced Materials Interfaces2196-73502024-10-011130n/an/a10.1002/admi.202400472Controlled Functionalization Strategy of Proteins Preserves their Structural Integrity While Binding to NanocarriersAna Mateos‐Maroto0Meiyu Gai1Maximilian Brückner2Volker Mailänder3Svenja Morsbach4Katharina Landfester5Max Planck Institute for Polymer Research Ackermannweg 10 55128 Mainz GermanyMax Planck Institute for Polymer Research Ackermannweg 10 55128 Mainz GermanyMax Planck Institute for Polymer Research Ackermannweg 10 55128 Mainz GermanyMax Planck Institute for Polymer Research Ackermannweg 10 55128 Mainz GermanyMax Planck Institute for Polymer Research Ackermannweg 10 55128 Mainz GermanyMax Planck Institute for Polymer Research Ackermannweg 10 55128 Mainz GermanyAbstract The use of proteins as targeting agents often requires their chemical modification for their efficient attachment to a given surface. However, no control over the protein integrity and functionality has been demonstrated to date. Chemical over‐modification causes the loss of the native structure of the protein and thus limits its targeting efficiency. To preserve structural integrity, a minimal modification strategy of proteins is developed while maintaining their functionality. Apolipoprotein A1 (ApoA1) and liposomes are utilized as a nanocarrier platform. Monitoring NHS ester chemistry by time‐of‐flight mass spectrometry experiments, the proposed functionalization route allows the effective chemical coupling of the minimally modified ApoA1 to the surface of the liposomes via a click chemistry reaction. The stability of the modified ApoA1 is ensured by analyzing the secondary structure by circular dichroism spectroscopy and the corresponding melting point by nano differential scanning fluorimetry. Furthermore, ApoA1 attachment to the liposomes is confirmed by flow cytometry experiments. The procedure presented in this study has the potential to be easily transferred to other proteins while introducing only minimally necessary chemical modifications to be covalently attached to different drug delivery platforms. This can help to improve their targeting efficiency for future biomedical applications.https://doi.org/10.1002/admi.202400472apolipoproteinliposomesnanocarriersprotein functionalization
spellingShingle Ana Mateos‐Maroto
Meiyu Gai
Maximilian Brückner
Volker Mailänder
Svenja Morsbach
Katharina Landfester
Controlled Functionalization Strategy of Proteins Preserves their Structural Integrity While Binding to Nanocarriers
Advanced Materials Interfaces
apolipoprotein
liposomes
nanocarriers
protein functionalization
title Controlled Functionalization Strategy of Proteins Preserves their Structural Integrity While Binding to Nanocarriers
title_full Controlled Functionalization Strategy of Proteins Preserves their Structural Integrity While Binding to Nanocarriers
title_fullStr Controlled Functionalization Strategy of Proteins Preserves their Structural Integrity While Binding to Nanocarriers
title_full_unstemmed Controlled Functionalization Strategy of Proteins Preserves their Structural Integrity While Binding to Nanocarriers
title_short Controlled Functionalization Strategy of Proteins Preserves their Structural Integrity While Binding to Nanocarriers
title_sort controlled functionalization strategy of proteins preserves their structural integrity while binding to nanocarriers
topic apolipoprotein
liposomes
nanocarriers
protein functionalization
url https://doi.org/10.1002/admi.202400472
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AT maximilianbruckner controlledfunctionalizationstrategyofproteinspreservestheirstructuralintegritywhilebindingtonanocarriers
AT volkermailander controlledfunctionalizationstrategyofproteinspreservestheirstructuralintegritywhilebindingtonanocarriers
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