Contents lists available at ScienceDirect Colloids and Surfaces B: Biointerfaces journal homepage: www.elsevier.com/locate/colsurfb Modulation of serum albumin protein corona for exploring cellular behaviors of fattigation-platform nanoparticles Van Hong Nguyen a,1 , Nilesh M. Meghani b,1 , Hardik H. Amin b , Thao T.D. Tran c,d , Phuong H.L. Tran e , Chulhun Park b , Beom-Jin Lee b, ⁎ a Pharmaceutical Engineering Laboratory, Biomedical Engineering Department, International University, Vietnam National University, Ho Chi Minh City, 70000, Vietnam b College of Pharmacy and Institute of Pharmaceutical Science and Technology, Ajou University, Suwon 16499, Republic of Korea c Department for Management of Science and Technology Development, Ton Duc Thang University, Ho Chi Minh City, Vietnam d Faculty of Pharmacy, Ton Duc Thang University, Ho Chi Minh City, Vietnam e Deakin University, Geelong Australia, School of Medicine ARTICLE INFO Keyword: Bovine serum albumin Cellular uptake Gelatin-oleic nanoparticles Lung cancer cells Protein-nanoparticle interaction Protein corona Albumin-precoated nanoparticles ABSTRACT Albumin is the most abundant protein in blood, and is the most frequently identified protein in the protein corona of nanoparticles (NPs). Thus, albumin plays an important role in modulating NPs’ physicochemical properties and bioavailability. In this study, the effect of bovine serum albumin (BSA) on gelatin-oleic nano- particles’ (GONs) physicochemical properties and cellular uptake were evaluated. Coumarin-6 was used as in- dicator to track the cellular uptake of GONs. The binding of BSA onto the GON surface increased the size, slightly reduced the negative net charge of the GON, and improved GON stability. The presence of BSA in cell culture media reduced the cellular uptake of BSA-uncoated GONs on human embryonic kidney cells 293 (HEK 293) and human adenocarcinoma alveolar basal epithelial cells (A549) in the media without FBS addition. Pre-coated BSA corona decreased cellular uptake of GONs in A549 cells in the media, with and without supplemented with 10% fetal bovine serum (FBS) but drastically increased cellular uptake on HEK 293 cells. BSA could be used to modulate protein corona as an endogenous ligand in NP design simply by mixing or incubating BSA with NPs before in vivo administration to inhibit or induce cellular uptake in specific cell types. 1. Introduction Three main strategies for cancer treatment are surgical removal of tumor, radiotherapy and chemotherapy. Recently, research on micro and nanoparticles targeted drug delivery systems have shown tre- mendous progress and enhanced hope to eradicate the tumor in vivo as well as in clinical studies [1,2]. In order to increase the success rate to treat the cancer by the nanoparticles, rigorous in vitro and in vivo evaluation studies are highly desired. After in vivo administration, nanoparticles (NPs) are affected by biological environments such as the pH, blood composition, temperature, and especially, proteins. Proteins adsorbed onto the NPs’ surface will create the bio-identity of the NPs, possibly changing their effectiveness. In the initial stage, proteins at high concentrations are adsorbed onto the surface; however, over time, they are replaced by higher affinity proteins, via Vroman’seffect [3,4]. The protein-NP complexes, not the NPs alone, control the circulation, allocation, biocompatibility, and bioavailability of the NPs. The ad- sorbed protein corona on each NP is unique, since they are the combined results of numerous factors, such as the protein composition and concentration, media pH, temperature, and fluidic states; and the physicochemical properties of the NPs, such as their size, shape, net charge, and surface chemistry [5–7]. Therefore, the designed formation of an adsorbed protein layer for NPs can alter biological outcomes [8,9]. Among a large number of blood proteins, albumin is the most abundant serum protein and is a prominent protein in the protein corona of various NPs. The binding of albumin increases the NPs’ size and neutralizes their charge [10,11]. Furthermore, albumin is also well known as a “dysopsonin”, which inhibits complement activation, re- duces phagocytosis, and improves the blood circulation time for na- nomaterials [12–14]. The addition of bovine serum albumin (BSA) at 5 mg/mL has shown to reduce the internalization of polystyrene NPs to 51% compared with that without BSA [15]. At the concentration of 3 mg/mL micelles prepared from hyaluronic-oleic conjugations, the cellular uptake of cancer cell line HCT-116 of these micelles decreased 80% with the presence of albumin at 50 mg/mL [16]. Moreover, https://doi.org/10.1016/j.colsurfb.2018.05.060 Received 23 January 2018; Received in revised form 3 April 2018; Accepted 26 May 2018 ⁎ Corresponding author. 1 These authors contributed equally to this work. E-mail address: bjl@ajou.ac.kr (B.-J. Lee). Colloids and Surfaces B: Biointerfaces 170 (2018) 179–186 Available online 28 May 2018 0927-7765/ © 2018 Elsevier B.V. All rights reserved. T