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

• Published in: Macromolecular bioscience 2019-10, Vol.19 (10), p.e1900145-n/a
• Main Authors: Guindani, Camila, Frey, Marie‐Luise, Simon, Johanna, Koynov, Kaloian, Schultze, Jennifer, Ferreira, Sandra R. S., Araújo, Pedro H. H., Oliveira, Débora, Wurm, Frederik R., Mailänder, Volker, Landfester, Katharina
• Format: Article
• Language: English
• Subjects: Animals; Binding; Biomolecules; Bovine serum albumin; Caproates - chemistry; Caproates - pharmacology; Cattle; Conjugates; Conjugation; Covalence; covalent conjugation; Flow cytometry; Fluorescence; fluorescence correlation spectroscopy; Fluorescence spectroscopy; HeLa Cells; Humans; Lactones - chemistry; Lactones - pharmacology; Macrophages; Nanoparticles; Nanoparticles - chemistry; Nanoparticles - ultrastructure; Organic chemistry; Particle Size; Proteins; Serum albumin; Serum Albumin, Bovine - chemistry; Serum Albumin, Bovine - pharmacology; thiol‐ene reaction; Transmission electron microscopy
• ISSN: 1616-5187; 1616-5195
• DOI: 10.1002/mabi.201900145

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. Poly(globalide‐co‐ε‐caprolactone) nanoparticles (NPs) are covalently conjugated with bovine serum albumin (BSA) by thiol‐ene coupling reaction. The success of the covalent conjugation is confirmed by flow cytometry and fluorescence correlation spectroscopy. Transmission electron microscopy enables the visualization of the protein layer surrounding the nanoparticles. BSA‐NPs conjugates present a reduced cell uptake by HeLa and macrophage cells, in comparison to uncoated NPs.