Mapping and identification of soft corona proteins at nanoparticles and their impact on cellular association

Abstract

The current understanding of the biological identity that nanoparticles may acquire in a given biological milieu is mostly inferred from the hard component of the protein corona (HC). The composition of soft corona (SC) proteins and their biological relevance have remained elusive due to the lack of analytical separation methods. Here, we identify a set of specific corona proteins with weak interactions at silica and polystyrene nanoparticles by using an in situ click-chemistry reaction. We show that these SC proteins are present also in the HC, but are specifically enriched after the capture, suggesting that the main distinction between HC and SC is the differential binding strength of the same proteins. Interestingly, the weakly interacting proteins are revealed as modulators of nanoparticle-cell association mainly through their dynamic nature. We therefore highlight that weak interactions of proteins at nanoparticles should be considered when evaluating nano-bio interfaces.

Effects of Surface Protein Adsorption on the Distribution and Retention of Intratumorally Administered Gold Nanoparticles

“…However, one of the most significant challenges associated with the translation of theranostic nanomedicine to the clinic is the interaction between the nanomaterial and the tumor microenvironment [ 3 ]. In particular, when nanoparticles enter a biological system, their interaction with proteins can lead to the formation of a protein corona adsorbed on their surface via electrostatic, hydrophobic, and van der Waals forces [ 4 ], which can alter particle stability [ 5 , 6 ], dispersibility [ 7 , 8 ], biodistribution [ 9 ], pharmacokinetics [ 10 , 11 , 12 ], and the toxicity profile [ 13 , 14 , 15 ].…”

Disentangling Biomolecular Corona Interactions With Cell Receptors and Implications for Targeting of Nanomedicines

“…Different methods have been developed to recover corona-coated nanoparticles, typically using centrifugation, size exclusion chromatography, magnetic extraction (for magnetic nanoparticles) or other similar approaches ( Cedervall et al, 2007b ; Docter et al, 2014 ; Bonvin et al, 2017 ; Francia et al, 2020 ). While in most cases it is only the hard corona to be recovered and characterized, more recently new methods based on field flow fractionation, in situ click chemistry and photo-affinity based chemoproteomics have been developed to characterize nanoparticles with both their hard and soft corona ( Weber et al, 2018 ; Mohammad-Beigi et al, 2020 ; Pattipeiluhu et al, 2020 ). Overall, it will be important for the field to address current limitations in isolating the protein corona in different laboratories and/or by using different methods ( Monopoli et al, 2013 ; Pisani et al, 2017 ).…”

Effect of Physico-Chemical Properties of Nanoparticles on Their Intracellular Uptake

“…There are several nanoparticle parameters that influence their uptake into the cells [44][45][46][47][48][49][50][51], and some recent studies exemplifying these are shown in Table 1. A brief overview of NP physicochemical properties and their impact on internalization is described below.…”

“…Since the biomolecules compete for the limited surface on NPs, at first NPs will be covered by more abundant small molecules, and subsequently replaced by the larger and high affinity molecules over time, to form the hard corona [80,81]. As shown in Scheme 3, two types of corona have been defined based on their structure: "hard" which can be formed when the biomolecules are irreversibly and directly bound to the NP surface, whereas "soft corona" consists of biomolecules that are reversibly bound to the hard corona or NP surface [47,78,79]. The lifetime of the hard corona has been shown to be several hours and it can define the NP surface properties.…”