核技术与纳米技术

第46卷第1期复旦学报(自然科学版)Vol. 46 No.12007年2月Journal of Fudan University( Natural Science )Feb. 2007Article ID :0427-7104( 2007 )01 -0011-10Nuclear Science Technology and Nano Science TechnologyCHAI Zhi-fang( Laboratory of Nuclear Analytical Techniques and Lab for Bio Environmental Health Sciences of Nanoscale Materials ,Muitidisciplinary Innoration Center ,Institute of High Energy Physics , Chinese Academy of Sciences ,Beijing 100039 .China )Abstract : Nuclear science and technology can play a unique role in nano science and technology，due to its nuclear charac-teristics and properties. In many cases nuclear science and technology can acquire intriguing results to help solve some basicscientific problems in nano science and technology , which are often difficult or even impossible for non - nuclear routes. Inthis review some latest achievements made in this aspect will be selectively introduced with the emphasis on the work donein our laboratory. The work includes( 1 ) nuclear reactions for synthesis of novel nanomaterials ;( 2 ) nuclear spectroscopyfor characterization of nanomaterials ; and( 3 ) nuclear analytical techniques for study of nanosafety and nanotoxicology.Some practical examples to demonstrate the roles of nuclear science and technology will be briefly described.Keywords : Nuclear Science Technology ; Nano Science Technology ; nuclear reactions ; nuclear analytical techniquesCLC number :O 571Document Code :ANuclear science and technology( NST，here after ) are based on nuclear properties , nuclear structures ,nuclear effects , nuclear reactions , and nuclear radiations that highly rely on nuclear spectroscopy and nuclearfacilities , like nuclear reactors and accelerators. Since the discovery of radioactivity by Becquerel at the end ofthe nineteenth century，over one hundred years have past. However , nano science and technology is an e-merging discipline and still at its infancy stage. The so called' Nano science and technologies" ( Nano-ST ,here after ) are the design , characterization , production and application of structures，devices and systems bycontrolling shape and size on the nanometer scale"'t 1]. Another definition of Nano-ST is that" Research and .technology development at the atomic , molecular or macromolecular levels , in the length scale of approximate-ly 1 - 100 nm range , to provide a fundamental understanding of phenomena and materials at the nanoscale andto create and use structures , devices and systems that have novel properties and functions because of theirsmall and/ or intermediate size"t2].More and more nuclear scientists are concerning about whether NST can play a unique role in nano-ST ?Or NST will be a must for Nano-ST ?Are nuclear theory , models and techniques able to provide unique meansto solve the issues being confronted in Nano-ST ?It is well known that the base of Nano-ST is nanostructured materials , i. e manufactured or engineeredmaterials with nano structures , like nano tube , nano wire , quantum dots , fullerene , etc. Of course ，thenano- sized oxides , compounds and metallic substances are also included.As the authoritative nuclear organization in the world , the International Atomic Energy Agency recentlyhosted a consultancy meeting with the topics on application of nuclear techniques in nanotechnology , whichstated that a radiation-based technology using X rays, γ ray中国煤化IIsandionbeamsisthekey to a variety of different approaches to nano-ST ,e.g. na:YHC N M H Gation ,nano drug deliv-ering systems , and nano machine ,etd 31.Received date : 2006- 12-04Biography :CHAI Zhi-fang male ,professor of physics Correspending author chaizf@ ihep. ac. cn.12复旦学报(自然科学版)第46卷1 Nuclear reaction for synthesis of novel nanomaterialsAn all- carbon fullerene dimer is a kind of fullerene derivative consisting of carbon atoms and two fullerenecages. They can be used in artificial photosynthesis , molecular device , new polymer , and supermolecularchemistry ,etc. Especially , odd- number all- carbon fullerene dimers C2m - -C- -C2m have unique characteristics.Traditionally , several non -nuclear synthetic methods are available , but most of them only for preparation ofeven-number carbon fullerene dimers( Tab. 1 ). Dragoe ,et al . developed a thermolysis of CooCBr2 with C6o at723 K for synthesis of C21 , but the experimental conditions are extremely difficult. In our laboratory ,a newnuclear method based on irradiation on nuclear reactor neutrons for synthesis of odd-number all carbonfullerene dimers was established 41].Tab. 1 Available methods for synthesis of all- carbon fullerene dimers#MethodC19C121C1zC130C140High temp & pressurey)High speed vibrationgrindingHigh temp. thermolysisY rayUV , visibleelectron“ Although some fllerene dimers have been reported , the odd-number all carbon Ci31 and Ci41 are notavailable ; only one report on Ci2( Dragoe ret al.1999 51); thermolysis of CoCBr2 with Co at 723 K. Noother C2m- -C- -C2m dimers have been reported.1 6941573CI4CislALUnnUusm/z12001300I40015001600170016001 7001 80019002000(a)(b)Fig.1 Spectra of MALDI TOF-MS of Ci31 and C41 produced by neutron iradiation ofraw C6o and C7o in nuclear reactor. The characteristic peaks of C131 andC141 in the spectra clearly existat m/z of 1 573 for Ci31 and 1 694 for C4[4]The specific nuclear parameters for the synthesis have been also studied , including the ratio of epithermalover thermal neutron flux and irradiation time. Very interestingly , fast neutrons are favorable to enhance theyield of the dimers. Besides Ci21 , this nuclear reaction can also produce C31 and C41 ,which are reported forthe first time in this field4]. Fig. 1 shows the spectra of MALDI TOF -MS of the products prepared by neu-tron iradiation of raw C60 and C7o , where the characteristic peaks of Ci31 and Ci41 are clearly identified. The .transmutation reactions induced by neutrons may be written中国煤化工Neutrons first transfertheir energies to fullerene cages via elastic and inelastic collisYHC N M H Greak the cages.n+ C6o→C+ n' ;C0→C1 or de-excited to C6o via vibration ;(1 )n+ C7o→C0+ n' ;C%→C1 or de-excited to C7o via vibration ;C6o+ Coo +Ci→C21 ;C6o + Czo+Cf→Cis1 ;C7o+C7o+ C*→Ci41.(2)This new nuclear method based on reactor neutron irradiation explores a new application field of NST，第1期CHAI Zhi- fang :Nuclear Science Technology and Nano Science Technology13which is able to synthesize other high carbon number fullrene dimers.The molecular structures of C121 , C131 and C141 have been intensively studied by high-resolution scanningtunneling microscopy ，" 'C nuclear magnetic resonance ，Fourier transformation-infrared absorption spec-troscopy , and other techniques ,which demonstrated that these new fullerene dimers feature a dumbbell-likestructure , instead of a large carbon cage 4]More interestingly , the novel carbon molecules of C2m - -C- -C2m type consisting of odd -numbered atomsC141 ,C131 ,C121 possess a novel functionalized nature ,i. e. a memory effect in transmutation processes of car-bon nanomolecules induced by neutron beams. The memory effect may provide new insights in finding practi-cal application of carbon nanomaterials. The results suggest that C60 or C7o cages can behave similar to not onlyan atom but also an atomic nucleus. We expect that the new nuclear method will not only open a new route toproduce a group of materials ,but even open a new utilization for advanced neutron sources in creating function-alized materials using electronically neutral beams , especially such organic nanomaterials that are difficult to begenerated through conventional approaches 4].We also found that Sc2@C84 or Sc2O3 could be" kicked" into cavities of SWNTs when a mixture of thescandium compound and SWNTs was bombarded by reactor neutrons at a relatively low temperature of about200 C. Fig. 2 shows its molcular structure. The method generated posibly a novel polymer [ -M@ C2m-SWNT- ] , and the first radioactive material encapsulated SWNTs ( emitting gamma-rays ), which arepromising nanoprobes for medical diagnosis and therapy at a cell level or molecular level. We discuss the newprocess of synthesizing the desired SWNT-based hybrid nanomaterials , and new subjects of studying interac-tions( and their consequences ) between subatomic particles and nanoparticles or molecules/ atoms being con-fined in a finite nanospaceTherefore，nuclear synthetic methods based on irradiation on neutrons , charged particles , photons , elec-trons and X-rays are providing a new route to prepare novel nano materials , including fullrene , metallo-fullerene ,single wall carbon tube , nano wire , nano tube and others. Another new and promising nucleartechnique is to adopt heavy ion bombardment for preparation of nano channels , nano pores or nano holes ,which are being applied in nucleic acid sequencing , single molecule detection , protein sensors , nano pump ,nano electrode and ion channels ,etc 7].Fig. 2 Molecular structure of[ Se2O, ]@SWNTf6]2 Nuclear spectroscopy for characterization of nanomaterialsV arious nuclear spectroscopic techniques can be applied to study physical and chemical characteristics ofnanomaterials , which mainly include the SR-based approachbsorption fine structurespectroscopy( EXAFS ), X-ray absorption near-edge structu中国煤化工), X-ray poeronspectroscopy( XPS) ,etc. A typical example to demonstrateTYHCNMH Gcopy in this aspect is touse XPS for identification of different Gd@C82 -containing compounds. The purpose of this work lies in possi-ble modulation of the electronic configurations of the innermost atoms inside a nanospace , nano sheath , withchemical modification ,in which systems of definite nanostructures were chosen. Systematic variations in ener-14复旦学报(自然科学版)第46卷gy ,intensity ,and widthof δ* and U* O1s core level spectra , in absorption characteristics of Cis fδ° transi-tion , in photo- absorption of pre edge and resonance regions of the Gd 4d-4f transition , were observed for Gd@C8t an isolated nanospace for Gd ) ,Gd@Cx( OH )X a modified nanospace for Gd ), and Gd@C&A OH)A( adifferently modified nanospace for Gd ) , and the reference materials Gd-DTPA( a semi-closed space for Gd )and Gd2O3. ( See Fig. 3 ) A sandwich- type electronic interaction along [ outer modification group ][ nanosheaths ]E[ inner metallic atom ] was observed in the molecules of modifications. This makes it possible to con-trol electron donation directions , either from the innermost metallic atom toward the outer nano sheaths or thereverse. The results suggest that one may effectively tune the fine structures of electronic configurations ofsuch a metallic atom being restricted into nano-structures through changing the number or identity of outergroups by chemical modifications. This may open a new route to realize the desirable designs for electronic andmagnetic properties of functionalized nanomaterials 8].Similar work has been reported for observing the energy shifts of actinides and transactinides by x- rayphotoelectron spectroscopy.More application fields in characterization of nanomaterials based on nuclear spectroscopy are foreseeablein future.3 Nuclear analytical techniques for study ofGd@Cx2(OH)22nanotoxicology(aNanotechnology is emerging as one of the key technologies1.1of the 215t century and is expected to enable developments1.across a wide range of sectors that can benefit citizens and im-1.2(b)Gd@Cx2(OH)2prove industrial competitiveness. Worldwide public investmentin research and development in nanotechnology ( R&D ) has .risen from around E 400 million in 1997 to some E3 billion in;0F200491. However ，there are concerns that some aspects of(cGd@Cez.5 Enanotechnology may introduce new health ，environmental and吕!social risks , which need to be addressed. Preliminary studieshave indicated some hazardous impact of nanomaterials on hu-号2.4 F(d)Gd- DTPAman healthf 10-12]. But some authors disagreed with the so-2.0 Fcalled nanotoxicology. Colvin recently stated": It is a mistake1.6 Ffor someone to say nanoparticles are safe ,and it is also a mis-take to say nanoparticles are dangerous. They are probably go-3.0十(e8Psnf[Gd2O;2.5 ting to be somewhere in the middle. And it will depend very6Dsn8Lmuch on the specifics"T131. Thus , at the moment systematicN 8Ponstudies from both sides of epidemical survey and molecular -level13014015060170180toxicological research are urgently required. In this case , nu-Photon Energy(eV)clear analytical techniques( NATs ) can play an important role 1。中国煤化sition spectra observed bysimply because of the inherent features of nuclear techniquesLation based XPSNATs refer to the analytical methods based on nuclearMYH. CNMHGbCdeC.OH)x;rameters，nuclear reactions ，nuclear effects , nuclear radia-(c)Gd@Cx ;( d )Gd-DTPA ;( e)Gd2O[8]tions , nuclear spectroscopy and nuclear facilities. Comparing The dash line is for easily examining the energy shiftwith non-nuclear techniques , NATs provide an independentof the resonance peaks between differentGd-containing compoundstool for assessment of toxic effects of nanomaerials. Generally ，第1期CHAI Zhi- fang :Nuclear Science Technology and Nano Science Technology1:NATs include neutron activation analysis , accelerator mass -spectrometry , scanning proton microprobe , iso-topic tracing( both radioactive and enriched stable isotopes ) , and synchronous radiation( SR )-based methods ,like SR-XRF , SR-EXAFS , and SR-XANES and others. The neutron diffraction spectroscopy and neutronscattering spectroscopy , especially by intensive pulsed neutron beams from spallation neutron facilities , can al-so be applied in nanosafety and nanotoxicology study , which can tell us where the atoms of interest are andwhat they are doing. The major merits of NATs lie in high sensitivity , good accuracy , high space resolutionand ability of in-situ and in vivo analysis. Particularly , NATs could identify the endogenous or exogenoussources of pollutants in environmental and biological systems. Quantification is another advantage of NATsthat is difficult or even impossible for non-nuclear techniques. In all NATs , radioisotope tracing is likely amost effective and indispensable method that has been widely used to study the in viwo quantitative distribu-tion of xenobiotics in recent decades.Generally ,NATs can answer the following scientific questions in nanosafety and nanotoxicology :Whether can nanomaterials( NMs ) enter organisms?If yes , how ?Whether is ( are ) there the target tissue( s) for NMs ?How do NMs distribute in tissues ?How about their subcellular distribution ?Whether can NMs bind with biological macromolecules ,e. g. proteins ?Whether can NMs pass through cell membranes ?Whether can NMs enter brain?If yes , how ?3.1 Localization of NMs in organismsIn fact ,as early as 1977 , Berry and his coworkers first reported the localization of nano gold particles ina pulmonary system by X- ray fluorescence technique , which clearly showed the presence of gold nanoparticles( 30 nm ) in platelets of a pulmonary capillary at 30 min after intratracheal itillation into rats 14]. Recently ,other authors used the same technical to examine the micro- distributions of nano particles in different organsand tissues ,e. g. nano Ni particles in human thrombus ; nanoparticles of Ti in human liver ; nano gold in liverfrom pharmacological therapy for knee joint arthrosis ; nano wear particle of dental amalgam in blood throm-bus ,etd15]However ,it should be pointed out that a technical obstacle should be solved ,i. e. the beam sizes of X-rayand charged particles are at about the micron level , which mean that the beam size is much bigger than thenano particles. Strictly speaking , the available micro- beam nuclear methods , per se ,are not suitable for nanoanalysis. In fact , the micro size beams could not give a real image at nano scale. Instead , they only show thescene of nano particles aggregation. Nowadays it is still hard to really achieve the localization analysis of nanoparticles in organisms. As an alternative , this technique can give a true image of nano particles in tissues onlycombined with other scanning nano- scale methods or the beam sizes are focused to a nano-level by electro-magnetic system improvement or other measures. Recently , a Dutch laboratory in the TU Eindhoven im-proved the beam-focusing system and could provide a beam of < < 100 nm size for proton- induced x- ray emissionanalysis 16]. Focused nano- beams of x -ray and charged particles are desirable in the near future for real local-ization of nano materials in biological and environmental samples.3.2 Translocation of NMs through biological barriersTranslocation study of NMs mainly includes the dermalMYH中国煤化工nd the bobraiorbar-rier. Translocation of NMs over cell membranes is also an excNMHGsess,butitisofendis-cussed in the interaction of NMs with cells. For this reason it will not be addressed in this section. Due to theunique merit to distinguish the sources of pollutants ,the isotopic tracer method , including radioactive isotopesand enriched stable isotopes , is becoming a powerful tool , even a must for this study.( 1 )Dermal translocation of nanomaterials16复旦学报(自然科学版)第46卷The epidermis is a tight barrier against penetration of foreign pollutants. Dermal translocation is minimalor nonexistent under normal conditions. But once in the dermis , lymphatic uptake is a major translocationroute , likely facilitated by uptake in dendritic cells ( epidermis ) and macrophages ; other potential pathwaysmay include the dense networks of blood circulation and sensory nerves in the dermis.(2 ) Translocation of nanomaterials in the respiratory tractIsotopic tracers can be used to trace how nanomaterials move in the respiratory tract and to see how theytransfer from nose finally to blood circulation system via pharynx , trachea , bronchi , alveolar and pulmonaryveins. Another important task is to observe pathways of particle clearance( disposition )in and out of the res-piratory tract. Available observations indicate that there are significant differences between nano- size particlesand larger particles for some of these pathways( 3 ) Translocation of nanomaterials in the brain. It is known that there are two ways for translocation of NMs through the brain barrier ,one is via the so-called blood brain barrier( BBB ) and the other is via the olfactory bulb. The former is via the blood circulationsystem , while the latter is via the respiratory tract. Knowledge on the cross BBB of NMs is not only scarce ,but also controversial. As to the olfactory bulb , more and more evidences provided by NATs indicate that in-haled nano particles are first deposited on the olfactory mucosa , then to olfactory bulb of the CNS by diffu-sion , similar to airborne' smell" molecules. Subsequent uptake and translocation of solid nano-particles alongaxons of the olfactory nerve has been demonstrated in non-human primates and rodents. More details will bediscussed in the section of 3. 6.However , as to the translocation of NMs in the blood circulation of human ,it is still ambiguous. Nem-mar et al. ( 2002a ) reported rapid appearance in the blood and significant accumulation of label in the liver ofhumans inhaling 99Tc-labeled 20 nm carbon particles 17]. But Brown net al . ( 2002 ) did not find any signifi-cant accumulation of the same isotope-labeled particles. At the moment the reasons for this discrepancy is un-cleat 181 Oberdoester ,et al. ( 2005 ) thought that the extent of extrapulmonary translocation of NMs washighly dependent on particle surface characteristics and physical and chemical behaviors , in addition to particlesizE19].3.3 Quantification of nanoparticles in organismsAs described above , the prominent advantage of NATs is to provide reliable quantitative information onNMs in organisms. A convincing example to show the ability of NATs in this aspect is an experiment of twinisotopes of 60Co and 57Co reported by Sabbioni ,et al[151. They used 60Co to label nano Co particles and 57Coto label cobalt sol. The former emits two γ raysof 1 173 and 1 332 keV , while other two γ rays of 122 and137 keV for the latter. Thus ,it becomes very easy to distingush these two different cobalt species by radiationdetection by a high purity germanium detector. The authors found a very fascinating phenomenon that therewas an obviously different accumulation of Co from Co-nano and Co-sol in Balb/3T3 cells in an in vitro ex-periemnt exposed for4 h to 100 pumol/Lof 57Co2+ and 6'Co-nano. The concentration of nano-Co inside thecells was 1 000 times higher than Co-sol. Further , their intracellular relative distribution patterns in the cellswere also evidently different. 62 % of nano-Co existed in nuclei , but only 24% for Co-sol. ( See Fig. 4) Theauthors claimed the possibility of accurate measurement of Co-nano in susDension and of the simultaneous de-termination of Co from Co-nano and Co-sol in the same sam中国煤化Inethod151.3.4 Study of biological distributions of nanomaterialsTYHCNMHGNATs are especially suited for study of absorption , distribution , metabolism , excretion and toxicology( ADME/T)of a pollutant in organisms. The same contribution in nanotoxicology study can be made byNATs. Liu' s group at Peking University first reported the biological distributions of single wall carbon nan-otubes( SWNTs ) in mice by 1251 labeling 20]. Authors found that 125 I labeled SWNTols administered to mice第1期CHAI Zhi- fang :Nuclear Science Technology and Nano Science Technology1NUCLEI (%)CYTOSOL (%)CELLULAR (%)Conano 62, Co2+ 24COnano15.6, Co-+ 35.8COmn 8.3, Co2i5.7LYSOSOMES + MITOCHONDRIA + MICROSOMES (%)Como14.1, Co2' 34.5Fig.4 Intracellular relative distributions of Co in Ballb/ 3T3 cells exposedfor4 h to 100 prmol/L of 57Co2+ and 60Co-nano( unit :% SI5distributed rapidly throughout the mouse body , with marked uptakes in the stomach , kidneys and bones( Fig.5). It is very inter esting that carbon nanotubes were observed to be very mobile in mice , behaving assmall active molecules , though their mean molecular weight is tremendously large , over 600 000. Negligibleradioactivity was detected in the brain , suggesting that the nanotubes were unable to pass through the blood-brain barrier. Radioactivity retained longest in the bones , and still could be detected at eleven days post dos-ing. It seemed that SWNTols were not acutely toxic at the dose tested , but they retained in the body for along time. This raises concerns about its chronic toxicity. The high affinity of SWNTols towards bone sug-gests its potential of being a drug delivery system for bone diseases.Similar work on study of biological distribution of nanomaterials labeled by other radioisotopes can refer to[e.g. 21 -24]NATs can also be utilized to study biological distributions of REE encapsuled fullerene. One example isprovided by Zhao et al. , who are using stable 169Tm to label C82 fullerene to form 169Tm@C82 , then deter-mine its distribution via neutron activation analysis of 169Tm10r( n ,Y ) reaction in nuclear reactof 251.ih3.5 Interactions of nanomaterials with cell and molecules8-d30There are a few reports available for study of interaction;d食6lldof nanomaterials with cell and biological macromolecules by 20NATs , which may be attributed to the experimental difficul-日 4ty. Donaldson and Tran ( 2002 ) proposed a hypothesis forcellular interaction of nano- particles , which included the fol-lowing steps : 1 ) the particle surface causes oxidative stressresulting in increased intracellular calcium and gene activa-tion ;2 ) transition metals released from particles result in ox .:MYH中国煤化工多有名名告CNM HGidative stress , increased intracellular calcium , and gene acti-Fig. 5 Biodistribution histogram for 1251vation; 3 ) cell surface receptors are activated by transition labeled SWNTols( 3.52x 10 cpm/mL ,15 r/mL )inmetals released from particles ，resulting in subsequent genemice at seven different time intervals after exposure.Data represent mean+STD( n=5920]activation; 4 ) intracellular distribution of nano- particles to18复旦学报(自然科学版)第46卷mitochondria generates oxidative stress. However ，the above process needs experimental evidence , which canbe likely achieved by NATs. Some schemes have been proposed in our laboratory for study of interaction ofmetallofullerene and carbon NTs with nucleic acids and proteins cell damage and translocation over cell mem-brane. Chen et al .( 2006 ) studied the interaction of 22 nm nano particle[ Gd@Csd OH )2 ] with glycophorinA by SR circular dichromatism and found that its secondary structure ( a -helix ) has been changed by the in-teractior( See Fig.6 ).同步辐射CD结果一Glycophorin A80 000Glycophorin A+Gd@Cx60 00040 00020 0000--20 0001807190 200 210 220 230*j240,17m-40 000-60 000222 nm-80000 L206 nmFig. 6 Spectrum of SR circular dichromatism for the interaction of 22 nm nano particle[ Gd@C&