SPRINGER BRIEFS IN MOLECULAR SCIENCE Yao He Yuanyuan Su Silicon Nano- biotechnology SpringerBriefs in Molecular Science For furthervolumes: http://www.springer.com/series/8898 Yao He Yuanyuan Su • Silicon Nano-biotechnology 123 YaoHe YuanyuanSu Instituteof FunctionalNanoand Soft Materials (FUNSOM), JiangsuKeyLaboratory forCarbon- BasedFunctional Materials &Devices andCollaborative InnovationCenter of SuzhouNanoScience andTechnology Soochow University Suzhou China ISSN 2191-5407 ISSN 2191-5415 (electronic) ISBN 978-3-642-54667-9 ISBN 978-3-642-54668-6 (eBook) DOI 10.1007/978-3-642-54668-6 Springer Heidelberg NewYork Dordrecht London LibraryofCongressControlNumber:2014934458 (cid:2)TheAuthor(s)2014 Thisworkissubjecttocopyright.AllrightsarereservedbythePublisher,whetherthewholeorpartof the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation,broadcasting,reproductiononmicrofilmsorinanyotherphysicalway,andtransmissionor informationstorageandretrieval,electronicadaptation,computersoftware,orbysimilarordissimilar methodology now known or hereafter developed. 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While the advice and information in this book are believed to be true and accurate at the date of publication,neithertheauthorsnortheeditorsnorthepublishercanacceptanylegalresponsibilityfor anyerrorsoromissionsthatmaybemade.Thepublishermakesnowarranty,expressorimplied,with respecttothematerialcontainedherein. Printedonacid-freepaper SpringerispartofSpringerScience+BusinessMedia(www.springer.com) Preface In the past decade, we have witnessed the giant advancement of silicon nanotechnology, which provides exciting new avenues for myriad electronic, energetic, environmental, biological, and biomedical applications. Among them, the exploration of silicon nanotechnology for bioapplications (so-called silicon nano-biotechnology) is one of the most important branches, receiving extensive attentions and revolutionizing basic research and clinical applications in recent years. Therefore, based on the previous elegant work of scientists worldwide and recent progress of our group, we publish this book that introduces silicon nanotechnology for biological and biomedical applications, particularly for biosensing, bioimaging, and cancer therapy. It is worthwhile to point out that, comparedtothesufficientlypublishedreports,onlylimitedreferencesarecitedhere duetothepagelimitation.Therefore,weexpressourapologiestoallthescientists whose research work is not introduced in this book. The present book may potentiallyserveasanewstartingpointintherealmofsiliconnano-biotechnology, andwillbeofinteresttoallchemists,materialscientists,aswellasbiologistsand clinicians. We express our sincere thanks to Prof. Shuit-Tong Lee for his generous help and invaluable suggestions. We are thankful to Mr. Fei Peng (a Ph.D. student underProf.YaoHe’ssupervision)forhiskindhelpintheelaborateandsystematic literature investigation. We appreciate the financial support from the National Basic Research Program of China (973 Program 2013CB934400 and 2012CB932400), the Funds for International Cooperation and Exchange of the National Natural Science Foundation of China (Grant No. 61361160412), the NaturalScienceFoundationofJiangsuProvinceofChina(GrantNo.BK20130052 and BK20130298), the Specialized Research Fund for the Doctoral Program of Higher Education of China (Grant No. 20133201110019 and 20133201120024), and a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD). Yao He Yuanyuan Su v Contents 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 1.1 Fabrication of Silicon Nanostructures. . . . . . . . . . . . . . . . . . . . 2 1.2 Biosensor. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 1.3 Bioimaging. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 1.4 Cancer Therapy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 1.5 Biosafety Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 2 Silicon Nanostructures. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 2.1 Fluorescent Silicon Nanoparticles . . . . . . . . . . . . . . . . . . . . . . 20 2.2 Silicon Nanowires. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24 2.2.1 Chemical Vapor Deposition . . . . . . . . . . . . . . . . . . . . . 26 2.2.2 Oxide-Assisted Growth . . . . . . . . . . . . . . . . . . . . . . . . 28 2.2.3 Metal-Catalyzed Electroless Etching . . . . . . . . . . . . . . . 28 2.3 Silicon Nanohybrid . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29 2.4 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 3 Silicon-Based Platform for Biosensing Applications. . . . . . . . . . . . 39 3.1 SiNWs-Based Electrochemical Biosensor. . . . . . . . . . . . . . . . . 40 3.1.1 SiNWs-Based Field-Effect Transistor . . . . . . . . . . . . . . 40 3.1.2 Amperometric-Based Biosensors. . . . . . . . . . . . . . . . . . 48 3.2 Silicon-Based Optical Biosensor . . . . . . . . . . . . . . . . . . . . . . . 50 3.2.1 Surface-Enhanced Raman Scattering-Based Biosensors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 3.2.2 Fluorescence-Based Biosensors. . . . . . . . . . . . . . . . . . . 51 3.3 Conclusions and Prospects . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54 4 Silicon-Based Nanoprobes for Bioimaging Applications. . . . . . . . . 61 4.1 In Vitro Imaging. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 4.2 In Vivo Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 4.3 Conclusions and Prospects . . . . . . . . . . . . . . . . . . . . . . . . . . . 70 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71 vii viii Contents 5 Silicon-Based Nanoagents for Cancer Therapy . . . . . . . . . . . . . . . 75 5.1 Chemotherapy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76 5.1.1 Drug Delivery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76 5.1.2 Protein and Gene Delivery. . . . . . . . . . . . . . . . . . . . . . 80 5.2 Silicon-Based Nanoagents for Phototherapy . . . . . . . . . . . . . . . 83 5.2.1 Photodynamic Therapy . . . . . . . . . . . . . . . . . . . . . . . . 84 5.2.2 Photothermal Therapy . . . . . . . . . . . . . . . . . . . . . . . . . 85 5.3 Conclusions and Perspectives . . . . . . . . . . . . . . . . . . . . . . . . . 87 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87 6 Biosafety Assessment of Silicon Nanomaterials . . . . . . . . . . . . . . . 93 6.1 SiNPs-Related Biosafety Assessment. . . . . . . . . . . . . . . . . . . . 94 6.2 Silicon Nanowires-Related Biosafety Assessment . . . . . . . . . . . 99 6.3 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101 7 Outlook. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105 7.1 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105 7.2 Challenges and Perspectives. . . . . . . . . . . . . . . . . . . . . . . . . . 107 Chapter 1 Introduction Nanotechnology has been widely regarded as one of the most important break- throughs since the last century, significantly revolutionizing science and tech- nology in the past several decades. As officially defined by the US National Nanotechnology Initiative in 2000, ‘‘Nanotechnology is concerned with materials and systems whose structures and components exhibits novel and significantly improved physical, chemical and biological properties, phenomena and processes due totheir nanoscalesize’’[1].Materials with at least onedimensionsizedfrom 1 to 100 nanometers (so-called nanomaterials) generally exhibit new and unique optical/electronic/magnetic merits, serving as essential and important tools for nanotechnology applications [2]. Thus far, various kinds of functional nanoma- terials (e.g., semiconductor nanomaterials, carbon nanomaterials, and silicon nanomaterials, etc.) have been well developed [1, 3–5], which offers exciting opportunities in virtually all branches of nanotechnology ranging from optical systems, electronic, chemical, and automotive industries, to environment, engi- neering, biology, and medicine. Among them, nanotechnology for biological and medicalapplications(generallydescribedas‘‘nano-biotechnology’’)isconsidered as one of the most important braches, which has shown great promise from basic research (e.g., investigation of complicated biological and biomedical processes that are hard to access with conventional approaches) to practical applications (e.g., early diagnosis and treatment of diseases) [5, 6]. Silicon is well-known as the crust’s second most abundant element on earth, only behind oxygen, providing a rich and low-cost resource support for myriad silicon-based applications. By virtue of its excellent semiconductor and mechan- ical properties, silicon materials act as the leading semiconductor materials and dominatetheelectronicsindustrytodate.Notably,novelstructural,opticalor/and electroniccharactersemergewhenthedimensionsofsiliconmaterialsarereduced to nanoscale level (so-called silicon nanomaterials) [7–9]. The last 20 years have witnessedthevastadvancement infabricating siliconnanomaterials andtherapid development of silicon nanomaterials-based applications in various fields, including electronics, energy, environment, biology, and biomedicine [10–12]. Takingadvantageofnon-orlowlytoxicpropertyofsilicon,explorationofsilicon nanotechnologyforbiologicalandbiomedicalapplicationsisofparticularinterest Y.HeandY.Su,SiliconNano-biotechnology,SpringerBriefsinMolecularScience, 1 DOI:10.1007/978-3-642-54668-6_1,(cid:2)TheAuthor(s)2014 2 1 Introduction Fig.1.1 Silicon nanobiotechnologyholds greatpromiseformyriad biologicalandbiomedical applications,particularlyfor biosensor,bioimaging,and cancertherapy,etc and has been extensively studied in recent years. This chapter presents an intro- duction of silicon nanomaterials, followed by a brief summary of silicon nano- technology for various bioapplications, particularly for biosensor, bioimaging, cancer diagnosis and therapy, etc. (Fig. 1.1). 1.1 Fabrication of Silicon Nanostructures Scientists have made an elegant work to successfully fabricate a great number of nanomaterials with well-defined structures and required functionality. To date, metal (e.g., silver and gold) nanostructures (e.g., nanoparticles, nanorods, and nanoshells)[13–15],fluorescentsemiconductorII–VIquantumdots(QDs)[16–19], carbon-based nanostructures (e.g., carbon nanotubes and graphene) [6, 20, 21], magneticnanoparticles(e.g.,Fe O nanoparticles)[22–24],andsiliconnanostruc- 3 4 tures(e.g.,siliconnanoparticlesandnanowires)[7,8,25]havebeenwelldeveloped. Siliconnanoparticles(SiNPs)andsiliconnanowires(SiNWs)arerecognizedas themostimportantzero-andone-dimensionalsiliconnanostructures,respectively. Of particular note, SiNPs whose sizes are generally smaller than *5 nm, exhibit relatively strong fluorescence due to effective recombination of electron and hole confined in nanodots, leading to a promising perspective of long-awaited optical applications [26, 27]. To date, several synthetic approaches have been well established for preparation of fluorescent SiNPs. Typically, in the 1990s, Ka- uzlarich and coworkers introduced a solution-phase reduction synthesis strategy, which is capable of mildly producing SiNPs at room temperature and normal 1.1 FabricationofSiliconNanostructures 3 atmospheric pressure [28]. Kortshagen et al. introduced a method titled plasma- assisted aerosol precipitation for high-yield synthesis of SiNPs with controllable sizes ranging from 2 to 8 nm [29]. In 2009, Lee et al. reported a electrochemical etchingmethod,allowingfabricationofmulticolorfluorescentSiNPswithtunable maximum emission wavelengths from 450 to 740 nm [30]. It is worthwhile to pointoutthat,mostoftheabove-mentionedSiNPsgenerallypossesspooraqueous dispersibility, thus requiring additional post-treatment or surface modification to renderthepreparedSiNPshydrophilicforbiologicalandbiomedicalapplications. To address this issue, He et al. recently developed novel microwave-assisted strategiestofacilelyanddirectlysynthesizehighlyfluorescentandwater-dispersed SiNPs in aqueous phase [31–33]. In particular, one of their latest studies dem- onstrated that the large-scale SiNPs with excellent aqueous dispersibility, strong fluorescence, and robust stability could be rapidly achieved (e.g., 0.1 SiNPs were yielded in 15-min microwave reaction) [33]. Ontheotherhand,avarietyofmethods(e.g.,chemicalvapordeposition(CVD) [34–38], oxide-assisted growth (OAG) [25, 39], and metal-catalyzed electroless etching [40–42], etc.) have been well established for preparation of SiNWs. Specifically,duetoelegantworkofLieber,Lee,Yang,etal.,CVDandOAG[25, 37–39]havebeenwidelyemployedastwomostpopularmeanstofabricateSiNWs and SiNWs arrays with high aspect ratio and production yield. Recently, Peng, Lee,etal.developedaclassofmetal-catalyzedelectrolessetchingapproach(e.g., HF-etching-assisted nanoelectrochemical method) [40–42], serving as an alterna- tivemethodtofacilelyproduceSiNWsinalow-costmanner.InadditiontoSiNPs and SiNWs, silicon-based nanohybrids featuring multifunctional properties are promising as powerful tools for various applications [43]. Figure 1.2 presents typical photographs and microscopical images of SiNPs, SiNWs, and SiNWs- basednanohybrids.SufficientdetailsconcerningthedesignofSiNPs,SiNWs,and their nanohybrids will be discussed in Chap. 2. 1.2 Biosensor Analysis and detection of chemical and biological species is of essential impor- tance for biomedical diagnosis, food safety, environment monitoring, and anti- bioterrorism, etc. [44]. A high-performance biosensor is expected to be highly sensitive, specific, reproducible, biocompatible, and capable of simultaneously multipletargetdetection.Inprinciple,twomodules,i.e.,arecognitionelementfor target binding and a transduction element for signaling the binding event are basically included in a sensor. Nowadays, a great deal of sensing devices can be commercially purchased. However, novel kinds of biosensors with sufficient sensitivity, high specificity, excellent reproducibility, and multiplexing detection capabilities still remain in high demand. Nanomaterials featuring unique physi- cochemical properties, serving as novel recognition or transduction elements, provide new possibilities for designing high-quality bioassay kits [45]. In