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University of Groningen Exploiting the Biomolecular Corona of Nanocarriers for Targeted drug Delivery to Endothelial Cells Aliyandi, Aldy

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University of Groningen

Exploiting the Biomolecular Corona of Nanocarriers for Targeted drug Delivery to Endothelial Cells

Aliyandi, Aldy

DOI:

10.33612/diss.133166778

IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below.

Document Version

Publisher's PDF, also known as Version of record

Publication date: 2020

Link to publication in University of Groningen/UMCG research database

Citation for published version (APA):

Aliyandi, A. (2020). Exploiting the Biomolecular Corona of Nanocarriers for Targeted drug Delivery to Endothelial Cells. University of Groningen. https://doi.org/10.33612/diss.133166778

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Exploiting the Biomolecular Corona of

Nanocarriers for Targeted Drug

Delivery to Endothelial Cells

Aldy Aliyandi

2020

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Paranymphs:

Simon Spahrkäs

Dulce Pamela Gonzalez Davila

Cover design: Aldy Aliyandi Layout design: Aldy Aliyandi Printed by: Proefschrift-AIO

ISBN: 978-94-93184-58-9

Copyright © 2020, Aldy Aliyandi

The research presented in this thesis was performed in the department of Nanomedicine and Drug Targeting at the Groningen Research Institute of Pharmacy (GRIP), University of Groningen, the Netherlands, and financially supported by GRIP and partly by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme under grant agreement No 637614 (NanoPaths). Printing of this thesis was

financially supported by the University Library and the Graduate School of Science and Engineering, Faculty of Science and Engineering, University of Groningen, the Netherlands

All right reserved. No part of this thesis may be reproduced in any form or by any means without prior permission of the author and the publisher holding the copyright of the published articles.

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Exploiting the Biomolecular Corona

of Nanocarriers for Targeted Drug

Delivery to Endothelial Cells

PhD Thesis

to obtain the degree of PhD at the University of Groningen

on the authority of the

Rector Magnificus Prof. C. Wijmenga and in accordance with

the decision by the College of Deans. This thesis will be defended in public on

Monday 5 October 2020 at 11.00 hours

by

Aldy Aliyandi

born on 2 December 1991 in Bandung, Indonesia

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Supervisors

Prof. A. Salvati Prof. I. S. Zuhorn

Assessment Committee

Prof. W. Parak Prof. G. Molema Prof. H. W. Frijlink

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Table of Contents

Chapter 1. General Introduction and Aim of the Thesis ...9

1.1 Nanomedicine ... 10

1.2 Endothelial cell barriers in nanomedicine ... 18

1.3 Aim of the thesis ... 20

References ... 24

Chapter 2. Disentangling Biomolecular Corona Interactions with Cell Receptors and Implications for Targeting of Nanomedicines ... 33

2.1 Introduction ... 34

2.2 The role of receptors in nanoparticle uptake ... 36

2.3 The role of the biomolecular corona in nanoparticle uptake ... 37

2.4 Methods to elucidate nanoparticle biomolecular corona-receptor interactions ... 40

2.5 Conclusions and future perspectives ... 49

References ... 51

Chapter 3. Effect of the Development of a Cell Barrier on Nanoparticle Uptake in Endothelial Cells ... 57

3.1 Introduction ... 58

3.2 Materials and methods ... 60

3.3 Results and discussion ... 67

3.4 Conclusions ... 78

Acknowledgements ... 79

References ... 81

Supplementary Information ... 88

Chapter 4. Effect of Endothelial Cell Heterogeneity on Nanoparticle Uptake ... 113

4.1 Introduction ... 114

4.2 Materials and methods ... 116

4.3 Results ... 121 4.4 Discussion ... 128 4.5 Conclusions ... 132 Acknowledgements ... 132 References ... 134 Supplementary Information ... 139

Chapter 5. Correlating Corona Composition and Cellular Uptake to Discover Proteins Directing Nanoparticles into Cells... 145

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5.1 Introduction ... 146

5.2 Materials and methods ... 148

5.3 Results and discussion ... 154

5.4 Conclusions ... 164

Acknowledgements ... 165

References ... 167

Supplementary Information ... 171

Chapter 6. Exploiting the Protein Corona to Identify Receptors for Targeting of Nanocarriers ... 179

6.1 Introduction ... 180

6.2 Materials and methods ... 182

6.3 Results and discussion ... 188

6.4 Conclusions ... 202

Acknowledgements ... 203

References ... 205

Supplementary Information ... 209

Chapter 7. General Discussion and Future Perspectives ... 227

References ... 238

Nederlandse Samenvatting ... 240

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