Seite - 96 - in Cancer Nanotheranostics - What Have We Learnd So Far?

Pearsonetal. Nanoparticlebiomoleculecorona FIGURE1 | (A)Formationof theNP-biomoleculecorona.Uponexposure to physiological fluids,NPsbecomecoatedwithavarietyofproteinsandother biomolecules.Thehardcorona iscomprisedof lowerabundance,highaffinity biomoleculeswithalmostnegligibleexchange rates.Thesoft corona is comprisedofmoreabundant, lesseraffinitybiomoleculeswith faster exchange rates. (B)Sizeandpoly(ethyleneglycol) (PEG)graftingdensity determinePEGconformationand total serumproteinadsorption toAuNPs. Reprintedwithpermission fromWalkeyetal. (2011).Copyright (2011) AmericanChemicalSociety.Negativeeffectof thebiomolecular coronaon the targeted interactionsofsilicaNPs. (C)Schematicofblocked targeted cellular interactionsof transferrin (Tf)-targetedNP in thepresenceofserum proteins. (D)MedianA549cell fluorescence intensityofTf-targetedNPs in variousconcentrationsofFBS. (C,D)Reprintedbypermission fromMacmillan PublishersLtd: [NatureNanotechnology] (Salvati et al., 2013), copyright2013. the corona, consisting of tightly and nearly irreversibly bound biomolecules. Atop the hard corona lie the “soft” corona layers that are composed of more leniently associated biomolecules classified by rapid exchange rates. With increasing time, less abundant, lessmobile, and higher binding affinity proteins will subsequently replace thehighlyabundant, loweraffinityproteins (Vroman effect) (Vroman et al., 1980).However, a recent study questioned the applicability of the Vroman effect to NPs and found that the composition of the hard corona was constant over time although the total amount of adsorbed proteins was changed (Tenzer et al., 2013). Properties ofNPs such as size and surfacehydrophobicityhavealsobeendemonstrated toaffect the composition and exchange rates of proteins such as transferrin (Tf)andalbumin(Ashbyetal., 2014). Although the formation of the biomolecular corona is unavoidable andplays a significant role in determining the bio- logicalbehaviorsofNPs, its importancehasonlyrecentlyreceived significant scientific attention. This mini review describes the importance of theNP-biomolecule corona on determining bio- logical responses, supported by a number of recently published reports. We will succinctly cover important aspects related to biomolecular corona formation, how it is influenced by various physicochemical properties of NPs, the impact of NPs on the structureofproteins, and the impactof thebiomolecular corona onthebiological interactionsofNPs. PHYSICOCHEMICALPROPERTIESOFNPsANDTHEIR EFFECTONBIOMOLECULARCORONAFORMATION The physicochemical properties of NPs determine the type of corona formed. Since the interactionsbetweenNPsandproteins occur at an interface, surface characteristics of NPs ultimately driveNP-biomolecule association. To better understand corona formation, many methods have been established (Monopoli et al., 2013;Bertoli et al., 2014).Using abioinformatics-inspired approach,Walkey et al., developed a protein corona fingerprint modelthataccountsfor64differentparameterstopredictthecel- lular interactions of NPs (Walkey et al., 2014). Thismodel was found to be 50%more accurate than pre-existing models that only consider size, aggregation state, and surface charge.Many material properties act in concert to drive biomolecular corona formation, in this section we will focus on the effect of size, surfacecharge,andhydrophobicity. It isgenerallyacceptedthatapositivecorrelationexists forNP size andprotein association. For example, a two-fold increase in proteinassociationwasmeasuredfor110nmsilverNPs(AgNPs), compared to 20nmAgNPs (Shannahan et al., 2013). However, an inverse correlationwas also reported between the amount of mouse serumprotein adsorbed and the size of 5, 15, and 80nm AuNPs (Martin et al., 2013). Itwas suggested that differences in curvature enabled a larger number of hydrophobic proteins to bindto thesmallerNPs in thiscase. Frontiers inChemistry | ChemicalEngineering November2014 |Volume2 |Article108 | 96