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MINIREVIEWARTICLE published:27November2014 doi: 10.3389/fchem.2014.00108 Biomolecularcoronaonnanoparticles:asurveyof recent literatureand its implications in targeteddrugdelivery RyanM.Pearson1,VanessaV.Juettner1 andSeungpyoHong1,2* 1 DepartmentofBiopharmaceuticalSciences,Universityof Illinois atChicago,Chicago, IL,USA 2DepartmentofBioengineering,Universityof IllinoisatChicago,Chicago, IL,USA Editedby: JoãoConde,Massachusetts InstituteofTechnology,USA Reviewedby: JoseMariaMontenegroMartos, UniversityofMarburg,Germany KennethA.Dawson,University CollegeDublin, Ireland *Correspondence: SeungpyoHong,Departmentof BiopharmaceuticalSciences, Universityof IllinoisatChicago,833 S.WoodSt.,Rm335,Chicago, IL 60612,USA e-mail: sphong@uic.edu Achieving controlled cellular responses of nanoparticles (NP) is critical for the successful developmentandtranslationofNP-baseddrugdeliverysystems.However,precisecontrol over the physicochemical and biological properties of NPs could become convoluted, diminished, or completely lost as a result of the adsorption of biomolecules to their surfaces.Characterizationoftheformationofthe“biomolecular”coronahasthusreceived increased attention due to its impact onNPand protein structure aswell as its negative effect onNP-based targeted drug delivery. This reviewpresents a concise survey of the recent literatureconcerning the importanceof theNP-biomolecule coronaandhow it can beutilized to improve the in vivoefficacyof targeteddeliverysystems. Keywords:nanoparticle,biomolecularcorona, targeteddrugdelivery, invivoefficacy INTRODUCTION Medical applicationsofnanoparticles (NPs)arewide-reachingas evidenced by their rapid development as therapeutic and diag- nostic agents (Peer et al., 2007; Zhang et al., 2008;Hubbell and Langer,2013). Inparticular, significantadvanceshavebeenmade in cancer therapybypursuingNPs as drugdelivery systems (Gu et al., 2007;Pearsonet al., 2012; vanderMeel et al., 2013), how- ever,manychallenges, especiallywith regard toachievingprecise control over nano-bio interactions, still remain to be addressed (Chauhan and Jain, 2013; Pearson et al., 2014). As increasingly morecomplexNPformulationsmove toward later stagesof clin- ical development, the need to understand and overcome those challenges isbecoming imminent. One of the most important challenges affecting NP-based drugdelivery is the formationof the “biomolecule”or “protein” corona (Cedervall et al., 2007). As NPs enter physiological flu- ids, proteins and other biomolecules such as lipids adsorb to their surfaceswith various exchange rates leading to the forma- tion of the biomolecular corona (Figure1A) (Nel et al., 2009; Monopoli et al., 2012; Saptarshi et al., 2013). As a consequence, the “synthetic identity” of theNP is lost and a distinct “biolog- ical identity” is acquired. This new identity governs how theNP is “seen” by cells and subsequently alters the way inwhichNPs interactwith cells. The compositionof the biomolecular corona isdynamicand ishighlydependentonthe initialbiological envi- ronment, indicating thepossibility of exposurememory (Milani etal.,2012).Opsoninadsorptionsuchas immunoglobulin(IgG), complement, and others contribute to the deteriorated in vivo propertiesofNPsbypromoting immunesystemrecognitionand rapid clearance from circulation. In contrast, dysopsonins such as albumin can coat NP surfaces and enhance their biological properties by reducing complement activation, increasing blood circulation time, and reducing toxicity (Peng et al., 2013). The bindingof lipids andother lipoproteins toNP surfaces can alter theuptakeand transportofNPs (Hellstrandet al., 2009).Taking these observations into consideration, the concept of the per- sonalized biomolecular corona has arisen, suggesting that NP coronas shouldbecharacterized inadisease specificmannerand notmerelybasedongeneralizationsobtained fromthe literature (Hajipouretal., 2014). While biomolecule adsorption alters many physicochemical propertiesof theNPsuchassize, shape,surfacecomposition,and aggregation state, NPsmay also induce conformational changes to the secondary structure of adsorbed proteins altering their biological activities (Monopoli et al., 2012). Inmany cases, pro- teinadsorptiontoNPscaninducefibrillation,immunosensitivity, andmisfolding, substantially altering properties such as biodis- tribution and circulation half-life, cellular uptake, intracellular localization, tumoraccumulation,andtoxicity(Linseetal.,2007; Aggarwal et al., 2009; Karmali and Simberg, 2011). Conversely, cases have demonstrated that biomolecule adsorption serves to protect the body from the toxicity of bare NPs, facilitating receptor-mediated interactions, and improvingpharmacokinetic profiles,whichdemonstrates itspotential advantages (Pengetal., 2013). Fundamental forces including electrostatic interactions, hydrogen bonding, hydrophobic interactions, and charge- transfer drive the association of biomolecules to the surface of NPs (Nel et al., 2009). A recent report by Tenzer et al., found that the biomolecular corona forms almost instantaneously (in less than30s) and is comprisedof almost 300differentproteins, althoughit typicallyconsistsofasimilarsetofproteins invarious quantities (Tenzer et al., 2013). However, it has been suggested thatNPscannotaccommodateasmanyproteinsontheirsurfaces anda significantly lowernumberofproteins arepresentbecause current analyses are performed over large numbers of NPs and represent macroscopic averages of protein composition (Monopoli et al., 2012). The “hard” corona is the first layer of www.frontiersin.org November2014 |Volume2 |Article108 | 95