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Bioanalytical Reviews Joachim Wegener Editor Measuring Biological Impacts of Nanomaterials 5 Bioanalytical Reviews Serieseditors Frank-MichaelMatysik,Regensburg,Germany JoachimWegener,Regensburg,Germany Aims and Scope BioanalyticalReviewsisthesuccessoroftheformerreviewjournalwiththesame name,anditwillcomplementSpringer’ssuccessfulandreputedreviewbookseries programintheflourishingandexcitingareaoftheBioanalyticalSciences. BioanalyticalReviews(BAR)publishesreviewscoveringallaspectsofbioanalytical sciences. It therefore is a unique source of quick and authoritative information for anybodyusingbioanalyticalmethodsinareassuchasmedicine,biology,biochemis- try,genetics,pharmacology,biotechnology,andthelike. Reviewsofmethodsincludeallmoderntoolsapplied,includingmassspectrometry, HPLC(initsvariousforms),capillaryelectrophoresis,biosensors,bioelectroanalysis, fluorescence, IR/Raman, and other optical spectroscopies, NMR radiometry, and methodsrelatedtobioimaging.Inparticulartheseriesvolumesprovidereviewson perspectivenewinstrumentalapproachesastheyapplytobioanalysis,andontheuse ofmicro-/nano-materials suchasmicro-and nanoparticles. Articlesonμ-totalana- lyticalsystems(μ-TAS)andonlabs-on-a-chipalsofallintothiscategory. Intermsofapplications,reviewsonnovelbioanalyticalmethodsbasedontheuseof enzymes,DNAzymes,antibodies, cellslices, tomentionthemoretypical ones, are highlywelcome.Articlesonsubjectsrelatedtotheareasincludinggenomics,prote- omics,metabolomics,high-throughputscreening,butalsobioinformaticsandstatis- ticsastheyrelatetobioanalyticalmethodsareofcoursealsowelcome.Reviewscover bothfundamentalaspectsandpracticalapplications. ReviewspublishedinBAR are(a)ofwiderscopeandauthorativelywritten(rather thanarecordoftheresearchofsingleauthors),(b)critical,butbalancedandunbiased; (c) timely, with the latest references. BAR does not publish (a) reviews describing establishedmethodsofbioanalysis;(b)reviewsthatlackwiderscope,(c)reviewsof mainlytheoreticalnature. More information about this series at http://www.springer.com/series/11663 Joachim Wegener Editor Measuring Biological Impacts of Nanomaterials With contributions by C. Bantz (cid:1) S. Beyazit (cid:1) D. Docter (cid:1) J. Domey (cid:1) M. Dwivedi (cid:1) K.A. Eslahian (cid:1) H.-J. Galla (cid:1) B. Goricnik (cid:1) I. Grau (cid:1) L. Haslauer (cid:1) K. Haupt (cid:1) I. Hilger (cid:1) N. Hinterreiter (cid:1) T. Hirsch (cid:1) C. Hupf (cid:1) R. Keller (cid:1) M. Kettering (cid:1) T. Lang (cid:1) M.-M. Lemberger (cid:1) S. Lukic (cid:1) M. Maskos (cid:1) J. Maximilien (cid:1) M. Oberleitner (cid:1) C. Rossi (cid:1) A.K. Sachan (cid:1) M. Sperber (cid:1) R. Sperling (cid:1) R. Stauber (cid:1) J.A. Stolwijk (cid:1) C. Strobel (cid:1) B. Tse Sum Bui (cid:1) J. Wegener Editor JoachimWegener UniversityofRegensburg Regensburg Germany ISSN1867-2086 ISSN1867-2094 (electronic) BioanalyticalReviews ISBN978-3-319-24821-9 ISBN978-3-319-24823-3 (eBook) DOI10.1007/978-3-319-24823-3 LibraryofCongressControlNumber:2016930554 SpringerChamHeidelbergNewYorkDordrechtLondon ©SpringerInternationalPublishingSwitzerland2016 Thisworkissubjecttocopyright.AllrightsarereservedbythePublisher,whetherthewholeorpartof the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilarmethodologynowknownorhereafterdeveloped. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publicationdoesnotimply,evenintheabsenceofaspecificstatement,thatsuchnamesareexempt fromtherelevantprotectivelawsandregulationsandthereforefreeforgeneraluse. Thepublisher,theauthorsandtheeditorsaresafetoassumethattheadviceandinformationinthis book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained hereinorforanyerrorsoromissionsthatmayhavebeenmade. Printedonacid-freepaper Springer International Publishing AG Switzerland is part of Springer Science+Business Media (www.springer.com) Preface Over the last two decades, nanotechnology has produced a myriad of different nanosizedstructureswithenormouslyinterestingmaterialpropertiesandpotential applications. Quantum dots (QDs), carbon nanotubes (CNTs), carbon dots (CDs), gold nanoparticles, and pigment particles are among the most well-known repre- sentatives.Butalsoless‘famous’nanomaterialsmadefrompolymers,noblemetals, or inorganic materials have raised considerable interest for applications in the biomedical field and other areas of our daily life. Despite of their undisputed usefulness in certain areas, there is a constant and justified concern that these nanomaterials may have unwanted biological effects on cells and organisms that have not yet been discovered and understood entirely. Thus, research into the biologicalimpactofnanoparticlesonhumanandanimalhealthaswellaspossible hazards for the environment is of outmost importance. As a deeper and more systematic understanding about the potential impact of nanomaterials on living cells,tissues,orecosystemsisinmanywaysbasedonstate-of-the-artbioanalytical techniques,thisvolumeofBioanalyticalReviewsisentirelydevotedtothistopic. The first chapter of the book, written by Eslahian and colleagues, provides a concise summary of the most prominent, highly tailored approaches to physically characterize nanomaterials. The various techniques are described in principle before their individual analytical performance is highlighted and critically com- pared to other methods. Special emphasis is placed on material characterization under physiological conditions to describe the particles as they are when they encounterbiologicalsystemslikecells,tissues,ororgans. The second chapter provided by Domey and coauthors addresses biochemical assaysthatareusedextensivelyinlabsaroundtheglobetostudythecytotoxictyor other cell responses to nanomaterials. Besides presenting model studies, this con- tribution critically highlights the pitfalls and possible artifacts that might be asso- ciated with these assays due to an interaction of the nanomaterials with the assay constituents. Often the possible artifacts can be accounted for by a carefully thought-outexperimentaldesignandpropercontrols.Buttheevidenceaccumulates thatlabel-basedassaysshouldbeusedwithgreatcaretoavoidmisleadingconclu- sionsfromcytotoxicitystudies. v vi Preface Followinguponthisdiscussionontheprosandconsoflabel-basedbiochemical assays to assess the impact of nanomaterials, the subsequent chapter by Sperber et al. discusses the use of label-free approaches for this purpose. After a more generalintroductiontothefieldoflabel-freedetectiontechniquesforcellobserva- tion,focusisplacedonimpedanceanalysisasoneofitsmajorrepresentatives.The chapter describes the general concept of impedance-based cell monitoring, intro- ducesthephysicalbackground,andillustratesitsperformanceonasetofexamples. Theseexampleshighlightthatnoninvasiveimpedancemeasurementscanbeusedto monitorahugevarietyofdifferentcell-basedassaysincludingtheanalysisofcell adhesionandproliferation,time-resolvedobservationofcytotoxicity,orthequan- titative examination of cell migration. After these introductory paragraphs, the articlesummarizesinhowfartheseassayshavebeenusedalreadytodescribethe impactofnanomaterialsonanimalcellsandtissuesattheseverydifferentpointsof cellphysiology.Inspiredbythepossibilitiesofimpedanceanalysistostudyonecell type subsequently in different physiological settings, the authors suggest a new perspective for nanotoxicology: instead of interpreting just one assay, we should establish response profiles for a given nanomaterial derived from a sequence of individualassays. As the airways are one major route of nanomaterial invasion into the human body, the fourth chapter addresses a set of model systems to study the impact of nanomaterialsonthealveolarlungsurfactantthatisliterallyofvitalimportanceto ourbreathingcycle.HereDwivedietal.describemodelsystemsfromsimplelipid monolayerstomorecomplexmodelsurfactantsandtheirresponsetonanoparticle encounter. The impact of nanoparticles on lipid organization is mostly demon- stratedbyLangmuirfilm-balancemeasurementsandstate-of-the-artmicroscopy. Asoneexampleofnanomaterialsthatdonotonlyraisehealthandenvironmental concerns but show very interesting bioanalytical applications, Lemberger et al. summarize inthe fifth chapter what is known about carbon nanodots (CDs), a member of the emerging class of photoluminescent carbon-based nanomaterials thatcanbeproducedfromrathersimpleandcheapstartingmaterialsusinglow-tech equipment. The various strategies of CD synthesis are grouped and discussed. Deeper inside the article, the authors provide a concise summary of the particles’ spectroscopicpropertiestogetherwiththeirmostestablishedbioanalyticalapplica- tionasalabelinmicroscopicimaging. The final chapter provided by Maximilien and coauthors takes it to the next level: nanomaterials as drug delivery vehicles in biomedicine. The authors start their discussion with lipid-based nanomaterials (liposomes) and their reversible loading with drugs. This discussion is followed by a concise overview of the availableinorganicnanoparticlesincludingquantumdots(QDs)andupconverting nanoparticles(UCNPs)withtheirinherentcapabilityofabsorbingtwoormoreNIR photonsbeforeaphotonofshorterwavelengthinthevisiblerange(higherenergy) isemitted.Thisupconversionhasseveraldistinctadvantages.Mostprominentlyit provides a fluorescence labeling of biological specimens without producing an unwanted and disturbing background fluorescence of biomolecules as the latter Preface vii requireexcitationbyUV/VIS.Thedescriptionofpolymericnanoparticlesasdrug deliveryvehiclesstartswithnanomaterialsmadefromnaturalpolymers.Withinthe class of nanoparticles produced from synthetic polymers, the authors highlight those materials that are either responsive to temperature, pH, or light because of their outstanding potential to allow for a localized unloading of the vehicle. The finalparagraphdescribespolymericnanoparticleswithimprintedrecognitionsites fordifferentlow-molecular-weightanalytes(MIPS)thatprovidemanynewoppor- tunitiesfornanoparticle-basedsensorsorthespecificseparationandenrichmentof complexsamples. The current volume of Bioanalytical Reviews presents a blend of different aspects that tackle the problem of measuring the biological impact of nanomaterials. This timely collection of articles will hopefully help to oversee the fast-developing field of nanotoxicology and emphasize its tight connection to bioanalysis. New instrumental developments, analytical assay formats, and new meansofdatadeconvolutionareneededtogetafewstepsclosertothebiggoalofa conceptual understanding about the bioresponse to nanoscale particles. This is particularly important as this topic is likely to stay relevant throughout the next decadesgiventheincreasingintegrationofnanomaterialsinourdailylives. Thisbookwouldnothavebeenpossiblewithoutthefineworkofallauthorsand coauthors to whom I would like to express my deepest gratitude. I hope you all agree that this big effort and the long hours of work have been worthwhile. Moreover, I would like to thank Dr. Rudolf Hutterer for his constant support in generalandtheeditorialpreparationofseveralchaptersinparticular. Regensburg(G)insummer2015. JoachimWegener ThiSisaFMBlankPage Contents CharacterizationofNanoparticlesUnderPhysiologicalConditions. . . 1 K.A.Eslahian,T.Lang,C.Bantz,R.Keller,R.Sperling,D.Docter, R.Stauber,andM.Maskos ProbingtheCytotoxicityofNanoparticles:ExperimentalPitfalls andArtifacts. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 JennyDomey,LisaHaslauer,InaGrau,ClaudiaStrobel, MelanieKettering,andIngridHilger MonitoringtheImpactofNanomaterialsonAnimalCellsby ImpedanceAnalysis:ANoninvasive,Label-Free,andMultimodal Approach. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 MichaelaSperber,ChristinaHupf,Michael-M.Lemberger,BarbaraGoricnik, NadjaHinterreiter,SonjaLukic,MaximilianOberleitner,JudithA.Stolwijk, andJoachimWegener InteractionofNanoparticleswithLipidMonolayersandLung SurfactantFilms. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109 MridulaDwivedi,AmitKumarSachan,andHans-JoachimGalla CarbonNanodots:Synthesis,Characterization,andBioanalytical Applications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135 Michael-M.Lemberger,ThomasHirsch,andJoachimWegener NanoparticlesinBiomedicalApplications. . . . . . . . . . . . . . . . . . . . . . 177 JacquelineMaximilien,SelimBeyazit,ClaireRossi,KarstenHaupt, andBernadetteTseSumBui Index. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211 ix