Contents lists available at ScienceDirect Materials Science & Engineering C journal homepage: www.elsevier.com/locate/msec On the formation of protein corona on colloidal nanoparticles stabilized by depletant polymers Romana Petry a,b, ⁎⁎ , Viviane M. Saboia a , Lidiane S. Franqui b,c , Camila de A. Holanda a , Thiago R.R. Garcia a , Marcelo A. de Farias b , Antonio G. de Souza Filho e , Odair P. Ferreira d , Diego S.T. Martinez b,c, ⁎⁎ , Amauri J. Paula a, ⁎ a Solid-Biological Interface Group (SolBIN), Department of Physics, Federal University of Ceará, P.O. Box 6030, 60455-900 Fortaleza, CE, Brazil b Brazilian Nanotechnology National Laboratory (LNNano), Brazilian Center for Research in Energy and Materials (CNPEM), Zip Code 13083-970 Campinas, São Paulo, Brazil c School of Technology, University of Campinas, Zip Code 13484-332 Limeira, Brazil d Laboratory of Advanced Functional Materials (LAMFA), Department of Physics, Federal University of Ceará, P.O. Box 6030, 60455-900 Fortaleza, CE, Brazil e Laboratory of Raman Spectroscopy, Department of Physics, Federal University of Ceará, P.O. Box 6030, 60455-900 Fortaleza, CE, Brazil ARTICLE INFO Keywords: Bovine serum albumin Pluronic F-127 Poly(ethylene glycol) Stöber silica nanoparticles Human blood plasma Protein corona Repulsive depletion forces ABSTRACT To counter the undesired colloidal destabilization of nanoparticles in biologically-compatible media of high ionic strength (i.e. NaCl, phosphate buffer), polymers can be added to nanoparticle suspensions that will be used in biomedical applications. In these suspensions, polymers can promote high colloidal stability by manifestation of steric and/or depletion forces. However, little is known about the influence of these polymers on the interactions between nanoparticles and the biological components of the organism, such as proteins and cells. In this work, it was shown that the addition of the polymers (i) Pluronic-F127 (PF127), (ii) polyethylene glycol (PEG) of dif- ferent molecular weights – 1.5, 12 and 35 kDa – and (iii) the protein bovine serum albumin (BSA) on colloidal silica nanoparticles (CSNPs; 135 nm) dispersed in phosphate-buffered saline (PBS) largely alter their colloidal stability through different mechanisms. Although all polymers were adsorbed on the CSNP surface, BSA main- tained the CSNP dispersion in the medium by electrosteric stabilization mechanisms, while PEG and PF127 led to the occurrence of depletion forces between the particles. In addition, it was found that the interactions between polymers and CSNPs did not prevent proteins to access the nanoparticles' surface and have minimal effect on the formation of the protein corona when they were incubated in human blood plasma. On the other hand, BSA had a greater effect on the CSNP protein corona profile compared to other polymers (PEG and PF127). Together, these results confirm that biocompatible polymers PEG and PF127 can be used as colloidal stabilizing agents for nanoparticles since they preserve the accessibility of biomolecules to the nanoparticle surface, and they have little effect on the protein corona composition. 1. Introduction Colloidal nanoparticles (CNPs) have been intensively studied in the last decade because of their promising applications in medicine, espe- cially due to their potential to carry drugs, to identify and transduce relevant biological signals, and to target specific biological sites [1,2]. More specifically, CNPs can act in tissue repair, diagnoses, drug de- livery, as imaging contrast agents, in cancer therapy and in many other ways [3–5]. Nevertheless, much remains to be studied about the effects and interactions of CNPs with biosystems of varying degrees of com- plexity, from biomacromolecules to organs [6,7,74]. In order to decrease the nanoparticle surface free energy, biomole- cules (e.g., proteins, peptides and glycolipids) largely adsorb on the nanoparticle surface when they are dispersed in biological fluids [9–12]. This nanoparticle capping, called protein corona, provides a “biological identity” to nanoparticles in the live organism which, in turn, dictates further interactions and processes [13,14]. As demon- strated in recent studies, the protein corona develops a dynamic be- havior as a function of the CNP composition, morphology, surface chemistry and reactivity, which comprise the nanoparticle features. On the other hand, important aspects are being neglected, such as the role of third-party interactions that might occur when CNP formulations are https://doi.org/10.1016/j.msec.2019.110080 Received 15 March 2019; Received in revised form 12 August 2019; Accepted 13 August 2019 ⁎ Correspondence to: A.J. Paula, Department of Physics, Federal University of Ceará, Campus do PICI, P.O. 3151, 60440-900 Fortaleza, CE, Brazil. ⁎⁎ Corresponding authors. E-mail addresses: romanapetry@gmail.com (R. Petry), diego.martinez@lnnano.cnpem.br (D.S.T. Martinez), amaurijp@fisica.ufc.br (A.J. Paula). Materials Science & Engineering C 105 (2019) 110080 Available online 13 August 2019 0928-4931/ © 2019 Elsevier B.V. All rights reserved. T