Covalently Binding of Bovine Serum Albumin to Unsaturated Poly(Globalide-Co-ε-Caprolactone) Nanoparticles by Thiol-Ene Reactions.

Camila Guindani,Pedro H H Araújo,Johanna Simon,Sandra R S Ferreira,Jennifer Schultze,Frederik R Wurm,Marie‐Luise Frey,Katharina Landfester,Kaloian Koynov,Débora Oliveira,Volker Mailänder

doi:10.1002/mabi.201900145

Abstract

When nanoparticles (NPs) are introduced to a biological fluid, different proteins (and other biomolecules) rapidly get adsorbed onto their surface, forming a protein corona capable of giving to the NPs a new "identity" and determine their biological fate. Protein-nanoparticle conjugation can be used in order to promote specific interactions between living systems and nanocarriers. Non-covalent conjugates are less stable and more susceptible to desorption in biological media, which makes the development of engineered nanoparticle surfaces by covalent attachment an interesting topic. In this work, the surface of poly(globalide-co-ε-caprolactone) (PGlCL) nanoparticles containing double bonds in the main polymer chain is covalently functionalized with bovine serum albumin (BSA) by thiol-ene chemistry, producing conjugates which are resistant to dissociation. The successful formation of the covalent conjugates is confirmed by flow cytometry (FC) and fluorescence correlation spectroscopy (FCS). Transmission electron microscopy (TEM) allows the visualization of the conjugate formation, and the presence of a protein layer surrounding the NPs can be observed. After conjugation with BSA, NPs present reduced cell uptake by HeLa and macrophage RAW264.7 cells, in comparison to uncoated NP. These results demonstrate that it is possible to produce stable conjugates by covalently binding BSA to PGlCL NP through thiol-ene reaction.

Highlights

The scientific and medical community has recognized that when nanoparticles (NPs) are exposed to a biological environment, serum albumin (BSA) by thiol-ene chemistry, producing conjugates which are resistant to dissociation
BSA was chosen as model protein for the covalent conjugation of a protein on the surface of PGlCL NPs via thiol-ene reaction
PGlCL nanoparticles were successfully conjugated with bovine serum albumin by thiol-ene reaction, producing BSA-nanoparticle conjugates, which are resistant to dissociation

Summary

Introduction

After conjugation with BSA, NPs present reduced cell uptake by HeLa and macrophage RAW264.7 cells, in comparison to uncoated NP These results demonstrate that it is possible to produce stable conjugates by covalently binding BSA to PGlCL NP through thiol-ene reaction. In this context, engineering the surface of the NPs is an excellent way to tune their interfacial properties and create a wide material platform for specific biological and biomedical applications.[6,7].

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