金納米與磁納米顆粒及其復(fù)合物的生物傳感和細(xì)胞成像研究
發(fā)布時間：2018-09-14 11:53
【摘要】：貴金屬納米顆粒具有獨特的表面等離子體共振(surface plasmon resonance, SPR)吸收和散射性質(zhì),已被廣泛用于生物傳感、細(xì)胞成像及癌癥治療等生物化學(xué)領(lǐng)域。而磁納米顆粒(MNPs),尤其是超順磁性四氧化三鐵(Fe304)納米顆粒,也在磁分離、磁馳豫開關(guān)、磁治療以及核磁共振成像(MRI)等生物醫(yī)學(xué)領(lǐng)域引起了人們廣泛關(guān)注。近年來,復(fù)合納米材料,特別是核殼結(jié)構(gòu)的納米材料,由于其能克服單一材料存在的穩(wěn)定性差、修飾較難、功能單一等缺陷,還能復(fù)合各種材料的性能,因而具有獨特的優(yōu)良性質(zhì)。其中,金納米包覆磁性納米復(fù)合顆粒(Fe3O4@Au)合成簡單、易修飾,且具有SPR和磁性雙重性質(zhì),體現(xiàn)了巨大的應(yīng)用潛力,已經(jīng)逐漸成為人們研究的焦點。然而,這些納米材料的應(yīng)用仍存在一些問題,例如生物分子如何有效調(diào)控金屬納米顆粒SPR性質(zhì),使其能更好的應(yīng)用于生物傳感以及疾病診斷和治療?納米材料在細(xì)胞膜表面是否具有防御病毒功能?多功能納米材料已有很多報道,但很少能集靶向、多模式成像及多治療手段于一身�；诖�,針對上述存在的問題,本文以金納米顆粒(AuNPs)、MNPs、以及Fe3O4@Au復(fù)合納米顆粒為代表,拓寬了其在生物傳感的應(yīng)用,分析了生物分子如何有效調(diào)控金屬納米顆粒等離子共振性質(zhì),以進(jìn)一步用于癌細(xì)胞成像與治療,并考察了納米材料修飾的細(xì)胞膜是否具有防御病毒功能。具體的研究內(nèi)容包括以下兩部分： 第一部分：基于AuNPs與MNPs在生物傳感中的應(yīng)用。利用AuNPs的SPR吸收性質(zhì),以正電AuNPs為探針實現(xiàn)了可視化檢測三磷酸腺苷(ATP)與堿性磷酸酶(ALP)；將核酸適配體aptamer)的高選擇性與MNPs磁性分離的性質(zhì)結(jié)合,利用銀納米顆粒(AgNPs)的SPR散射性質(zhì),建立了高靈敏、高選擇性地測定溶菌酶(lysozyme)的方法�？疾炝松锓肿尤绾斡行д{(diào)控貴金屬納米顆粒SPR性質(zhì)。具體工作如下： 1.ATP誘導(dǎo)正電AuNPs聚集的光學(xué)性質(zhì)研究及定量檢測ATP。實驗發(fā)現(xiàn),通過調(diào)節(jié)ATP濃度,可以有效調(diào)控AuNPs在可見區(qū)的SPR吸收性質(zhì)。提出了ATP與AuNPs的作用主要通過兩種方式：首先是ATP的磷酸根與AuNPs表面陽離子表面活性劑之間的靜電作用,其次是金原子與ATP含N堿基之問的配位作用�；贏uNPs的SPR吸收用于定量檢測ATP,方法簡單、成本較低、耗時較短、選擇性好,檢測限達(dá)到0.82μM。進(jìn)一步實驗發(fā)現(xiàn),ATP的類似物包括GTP, UTP, CTP, ADP,AMP等,誘導(dǎo)AuNPs聚集程度各不相同,由此可建立了一種簡單的可視化分析方法區(qū)分ATP類似物。 2.ALP經(jīng)過脫磷酸化反應(yīng)使ATP轉(zhuǎn)化為腺苷,建立了一種基于AuNPs的免標(biāo)記可視化方法檢測ALP。該方法的檢測范圍可以通過加入金屬離子動態(tài)調(diào)節(jié),加入Ca2+或Pb2+可以使其線性范圍從100-600unit/L分別調(diào)節(jié)至5.0-100unit/L及0.2-20unit/L,靈敏度得到極大提高。該方法具有高選擇性、高靈敏度、檢測范圍動態(tài)可調(diào)的優(yōu)點,用于檢測人血清樣品中ALP含量,與臨床結(jié)果一致。 3. Aptamer偶聯(lián)MNPs用于lysozyme的富集與高靈敏分析檢測。建立了一種基于MNPs與aptamer作為高選擇性的分離富集載體,AgNPs作為散射信號探針的方法用于檢測lysozyme。首先利用MNPs與aptamer偶聯(lián)復(fù)合物特異性分離并富集lysozyme,再根據(jù)其正電荷性質(zhì),可與檸檬酸根包被的AgNPs通過靜電作用結(jié)合,磁性分離上清液中AgNPs強(qiáng)烈的表面等離子共振散射光降低,可用于定量分析lysozyme。磁性分離下層吸附的AgNPs具有強(qiáng)烈的暗場散射光,可用暗場敞射成像對lysozyme進(jìn)行半定量分析。方法結(jié)合了aptamer的高選擇性以及l(fā)ysozyme帶正電荷的兩個性質(zhì),為測定lysozyme設(shè)下雙重開關(guān),能提高方法的選擇性及測定結(jié)果的準(zhǔn)確性。以具有強(qiáng)散射信號的AgNPs作為信號探針,可以提高方法靈敏度,檢測限可低至0.1nM。該方法設(shè)計具有普遍適用性,對于復(fù)雜樣品的測定具有重要意義。 第二部分：MNPs與Fe3O4@Au復(fù)合納米顆粒在細(xì)胞成像中的應(yīng)用。首先,以MNPs為例,考察了在細(xì)胞膜表而構(gòu)建“鐵籠子”是否具有防御病毒入侵的功能,拓寬了磁納米材料在細(xì)胞成像及生物醫(yī)學(xué)方而的應(yīng)用。其次,我們結(jié)合了Au與Fe3O4各自優(yōu)越的性能,制備成復(fù)合納米顆粒,修飾靶向配體,構(gòu)建了Fe3O4@Au多功能納米材料用于癌細(xì)胞的靶向多模式成像與治療。具體工作如下： 1.細(xì)胞膜表面構(gòu)建“鐵籠子”用于抗病毒入侵。本文使用人喉癌上皮細(xì)胞(HEp-2),探討了細(xì)胞膜外形成網(wǎng)狀“鐵籠子”是否能抑制呼吸道合胞病毒(RSV)的感染。MNPs可通過鏈霉親和素與生物素的特異性反應(yīng)吸附到細(xì)胞膜表面,利用顆粒表面修飾DNA的多價效應(yīng),通過雜交形成網(wǎng)狀“鐵籠子”,期望達(dá)到抑制病毒入侵的效果。實驗采用掃描電鏡(SEM)證實了“鐵籠子”在細(xì)胞膜表面形成。其具有良好的生物相容性,能在一定程度上防御病毒侵染細(xì)胞。當(dāng)病毒侵染MOI值為2時,有“鐵籠子”保護(hù)的細(xì)胞,其細(xì)胞存活率能從24.1士4.4%提高到49.0±10.0%。利用免疫熒光顯微技術(shù),表明“鐵籠子”抑制病毒入侵可能通過以下兩種方式：其空間位阻效應(yīng)阻礙了病毒與細(xì)胞膜的結(jié)合；降低細(xì)胞膜柔韌性,抑制病毒出胞以及在細(xì)胞間的擴(kuò)散。本文利用納米材料在一定程度上實現(xiàn)抗病毒入侵,為開發(fā)新的抗病毒藥物以及其它防治病毒性疾病的新方法研究提供了思路。 2.多功能Fe3O4@Au核殼納米花靶向癌細(xì)胞雙模式成像與治療。發(fā)展能結(jié)合診斷與治療于一身的多功能納米材料在分子醫(yī)學(xué)領(lǐng)域有極其重要的意義。本文將五個獨特的功能有機(jī)地整合到了一個粒徑為70nm的Fe3O4@Au納米花上。Fe304核可作為MRI顯影劑；表面包被金殼,使其具有近紅外吸收,產(chǎn)生光熱效應(yīng)使細(xì)胞溫度升高,可用于光熱治療。高溫能促進(jìn)負(fù)載的抗癌藥物鹽酸阿霉素(Dox)快速釋放,產(chǎn)生紅色熒光,可通過共聚焦熒光顯微鏡監(jiān)測其釋放過程。顆粒表面偶聯(lián)aptamer可提高藥物的靶向釋放。該Fe3O4@Au多功能納米材料結(jié)合了熒光成像與MRI雙模式成像方式,可提高癌細(xì)胞診斷準(zhǔn)確性,并有利于監(jiān)測藥物釋放。當(dāng)納米材料負(fù)載0.8μM Dox時達(dá)到的治療效果,可與單獨使用2.0μM Dox時相當(dāng)。因此,將化療與光熱治療結(jié)合使用,可以減少藥物用量,降低非特異性的毒副作用�？傊�,該多功能納米材料同時具有靶向、雙模式成像與雙治療手段結(jié)合的功能,對生物醫(yī)學(xué)領(lǐng)域,尤其是癌癥治療具有潛在的意義。 總之,本論文具有以下三個創(chuàng)新點：(一)利用生物分子實現(xiàn)了對金屬納米顆粒SPR性質(zhì)的有效調(diào)節(jié)。(二)構(gòu)建了與傳統(tǒng)的小分子設(shè)計不同的病毒防御系統(tǒng),以磁納米顆粒在細(xì)胞膜表面形成“鐵籠子”抗病毒侵染。(三)制備了同時具有靶向、雙成像模式及雙治療手段五個功能的多功能納米材料。該研究論文拓寬了金屬納米顆粒在化學(xué)與生物傳感方面的應(yīng)用,對于將金屬納米顆粒進(jìn)一步應(yīng)用于細(xì)胞成像及光熱治療領(lǐng)域提供了一定依據(jù),在癌細(xì)胞診斷與治療方面具有一定的臨床價值。
[Abstract]:Noble metal nanoparticles have unique surface plasmon resonance (SPR) absorption and scattering properties, and have been widely used in biochemical fields such as biosensors, cell imaging and cancer therapy. In recent years, composite nanomaterials, especially core-shell nanomaterials, have attracted much attention due to their ability to overcome the shortcomings of single materials, such as poor stability, difficult modification, single function, and composite properties of various materials. Among them, gold nanoparticles coated with magnetic nanoparticles (Fe3O4@Au) are easy to modify, and have the dual properties of SPR and magnetism. It has become the focus of research. However, there are still some problems in the application of these nanomaterials, such as how biological molecules effectively regulate gold. As a kind of SPR nanoparticles, nanoparticles can be used in biosensors, disease diagnosis and treatment. Does nanomaterials have the ability to defend against viruses on the surface of cell membranes? Many reports have been reported on multifunctional nanomaterials, but few of them can be combined with targeting, multimodal imaging and multimodal therapy. The applications of AuNPs, MNPs and Fe3O4@Au composite nanoparticles in biosensors have been broadened. The effective regulation of plasma resonance properties of metal nanoparticles by biological molecules has been analyzed for further application in cancer imaging and treatment. The defense of cell membranes modified with nanomaterials has been investigated. The specific research contents include the following two parts:
The first part is based on the application of AuNPs and MNPs in biosensors.Using the SPR absorption property of AuNPs and the positively charged AuNPs as the probe, the visual detection of ATP and ALP was realized.The highly selective aptamer was combined with the magnetic separation property of MNPs and the SPR dispersion of AgNPs was utilized. A highly sensitive and selective method for the determination of lysozyme was developed. The effective regulation of SPR properties of noble metal nanoparticles by biological molecules was investigated.
1. Optical properties of ATP-induced aggregation of positive AuNPs and quantitative detection of ATP. It was found that the SPR absorption properties of AuNPs in the visible region could be effectively regulated by adjusting the ATP concentration. It was proposed that the interaction between ATP and AuNPs could be achieved by two ways: first, the electrostatic interaction between ATP phosphate and surface cationic surfactants of AuNPs. SPR absorption based on AuNPs can be used to quantitatively detect ATP. The method is simple, cost-effective, time-consuming and selective. The detection limit is 0.82 mu M. Further experiments show that the analogues of ATP, including GTP, UTP, CTP, ADP, AMP and so on, induce the aggregation degree of AuNPs to be different, which can be established. A simple visual analysis method is used to distinguish ATP analogues.
2. After dephosphorylation, ATP was converted into adenosine. A label-free visualization method based on AuNPs was established to detect ALP. The detection range of this method can be adjusted dynamically by adding metal ions. The linear range of the method can be adjusted from 100-600 unit/L to 5.0-100 unit/L and 0.2-20 unit/L by adding Ca2+ or Pb2+ respectively, and the sensitivity can be obtained. This method has the advantages of high selectivity, high sensitivity and dynamic adjustable detection range. It is used to detect the content of ALP in human serum samples, which is consistent with clinical results.
3. Aptamer-coupled MNPs were used for lysozyme enrichment and highly sensitive detection. A method based on MNPs and aptamer as highly selective separation and enrichment carriers and AgNPs as scattering signal probes was developed for lysozyme detection. The strong surface plasmon resonance scattering light of AgNPs in the supernatant of magnetic separation can be used for quantitative analysis of lysozyme. Considering the high selectivity of aptamer and the two properties of lysozyme with positive charge, a double switch for the determination of lysozyme can improve the selectivity of the method and the accuracy of the determination results. AgNPs with strong scattering signal can be used as a signal probe to improve the sensitivity of the method, and the detection limit can be as low as 0.1nM. The design of the method is generally applicable. It is important for the determination of complex samples.
The second part is the application of MNPs and Fe3O4@Au composite nanoparticles in cell imaging. Firstly, taking MNPs as an example, we investigated whether the "iron cage" constructed on the surface of cell membrane has the function of preventing virus invasion, which broadens the application of magnetic nanomaterials in cell imaging and biomedicine. Secondly, we combined the advantages of Au and Fe3O4. Fe3O4 @ Au multifunctional nanomaterials were prepared to be used in targeted multimodal imaging and therapy of cancer cells.
1. An iron cage was constructed on the surface of the cell membrane to resist virus invasion. In this paper, the human laryngeal carcinoma epithelial cells (HEp-2) were used to investigate whether the reticulated iron cage could inhibit the infection of respiratory syncytial virus (RSV). Surface-modified DNA has a multivalent effect, which is expected to inhibit viral invasion by hybridization. Scanning electron microscopy (SEM) was used to confirm the formation of "iron cage" on the surface of cell membrane. The survival rate of the cells protected by the cage was increased from 24.1 to 4.4% to 49.0 (+ 10.0%). Immunofluorescence microscopy showed that the cage could inhibit virus invasion in two ways: steric hindrance hindered the binding of the virus to the cell membrane, decreased the flexibility of the cell membrane, inhibited the emergence of the virus, and inhibited the viral invasion. In this paper, nano-materials are used to achieve anti-virus invasion to a certain extent, which provides ideas for the development of new antiviral drugs and other new methods for the prevention and treatment of viral diseases.
2. Multifunctional Fe3O4@Au core-shell nanoflowers are targeted at cancer cells by dual-mode imaging and therapy. The development of multifunctional nanomaterials combining diagnosis and therapy is of great significance in the field of molecular medicine. High temperature can promote the rapid release of doxorubicin hydrochloride (Dox), a loaded anticancer drug, and produce red fluorescence. The release process can be monitored by confocal fluorescence microscopy. Targeted drug release. The Fe3O4@Au multifunctional nano-material combines fluorescence imaging with dual-mode MRI imaging to improve the diagnostic accuracy of cancer cells and facilitate monitoring drug release. The therapeutic effect achieved when the nano-material is loaded with 0.8 mu mDox is comparable to that achieved when 2.0 mu mDox is used alone. Therefore, chemotherapy and photothermal therapy are combined. In a word, this multifunctional nano-material has the function of targeting, dual-mode imaging and dual-therapy, which has potential significance for biomedical field, especially cancer treatment.
In summary, this paper has three innovations: (1) The SPR properties of metal nanoparticles can be effectively regulated by using biological molecules. (2) A virus defense system different from traditional small molecule design was constructed to form "iron cage" on the surface of the cell membrane to resist virus infection. (3) Targeted metal nanoparticles were prepared. This paper extends the application of metal nanoparticles in chemical and biosensor fields, provides a certain basis for further application of metal nanoparticles in cell imaging and photothermal therapy, and has a certain extent in cancer cell diagnosis and treatment. Clinical value.
【學(xué)位授予單位】：西南大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2013
【分類號】：R318.08;TB383.1
[Abstract]:Noble metal nanoparticles have unique surface plasmon resonance (SPR) absorption and scattering properties, and have been widely used in biochemical fields such as biosensors, cell imaging and cancer therapy. In recent years, composite nanomaterials, especially core-shell nanomaterials, have attracted much attention due to their ability to overcome the shortcomings of single materials, such as poor stability, difficult modification, single function, and composite properties of various materials. Among them, gold nanoparticles coated with magnetic nanoparticles (Fe3O4@Au) are easy to modify, and have the dual properties of SPR and magnetism. It has become the focus of research. However, there are still some problems in the application of these nanomaterials, such as how biological molecules effectively regulate gold. As a kind of SPR nanoparticles, nanoparticles can be used in biosensors, disease diagnosis and treatment. Does nanomaterials have the ability to defend against viruses on the surface of cell membranes? Many reports have been reported on multifunctional nanomaterials, but few of them can be combined with targeting, multimodal imaging and multimodal therapy. The applications of AuNPs, MNPs and Fe3O4@Au composite nanoparticles in biosensors have been broadened. The effective regulation of plasma resonance properties of metal nanoparticles by biological molecules has been analyzed for further application in cancer imaging and treatment. The defense of cell membranes modified with nanomaterials has been investigated. The specific research contents include the following two parts:
The first part is based on the application of AuNPs and MNPs in biosensors.Using the SPR absorption property of AuNPs and the positively charged AuNPs as the probe, the visual detection of ATP and ALP was realized.The highly selective aptamer was combined with the magnetic separation property of MNPs and the SPR dispersion of AgNPs was utilized. A highly sensitive and selective method for the determination of lysozyme was developed. The effective regulation of SPR properties of noble metal nanoparticles by biological molecules was investigated.
1. Optical properties of ATP-induced aggregation of positive AuNPs and quantitative detection of ATP. It was found that the SPR absorption properties of AuNPs in the visible region could be effectively regulated by adjusting the ATP concentration. It was proposed that the interaction between ATP and AuNPs could be achieved by two ways: first, the electrostatic interaction between ATP phosphate and surface cationic surfactants of AuNPs. SPR absorption based on AuNPs can be used to quantitatively detect ATP. The method is simple, cost-effective, time-consuming and selective. The detection limit is 0.82 mu M. Further experiments show that the analogues of ATP, including GTP, UTP, CTP, ADP, AMP and so on, induce the aggregation degree of AuNPs to be different, which can be established. A simple visual analysis method is used to distinguish ATP analogues.
2. After dephosphorylation, ATP was converted into adenosine. A label-free visualization method based on AuNPs was established to detect ALP. The detection range of this method can be adjusted dynamically by adding metal ions. The linear range of the method can be adjusted from 100-600 unit/L to 5.0-100 unit/L and 0.2-20 unit/L by adding Ca2+ or Pb2+ respectively, and the sensitivity can be obtained. This method has the advantages of high selectivity, high sensitivity and dynamic adjustable detection range. It is used to detect the content of ALP in human serum samples, which is consistent with clinical results.
3. Aptamer-coupled MNPs were used for lysozyme enrichment and highly sensitive detection. A method based on MNPs and aptamer as highly selective separation and enrichment carriers and AgNPs as scattering signal probes was developed for lysozyme detection. The strong surface plasmon resonance scattering light of AgNPs in the supernatant of magnetic separation can be used for quantitative analysis of lysozyme. Considering the high selectivity of aptamer and the two properties of lysozyme with positive charge, a double switch for the determination of lysozyme can improve the selectivity of the method and the accuracy of the determination results. AgNPs with strong scattering signal can be used as a signal probe to improve the sensitivity of the method, and the detection limit can be as low as 0.1nM. The design of the method is generally applicable. It is important for the determination of complex samples.
The second part is the application of MNPs and Fe3O4@Au composite nanoparticles in cell imaging. Firstly, taking MNPs as an example, we investigated whether the "iron cage" constructed on the surface of cell membrane has the function of preventing virus invasion, which broadens the application of magnetic nanomaterials in cell imaging and biomedicine. Secondly, we combined the advantages of Au and Fe3O4. Fe3O4 @ Au multifunctional nanomaterials were prepared to be used in targeted multimodal imaging and therapy of cancer cells.
1. An iron cage was constructed on the surface of the cell membrane to resist virus invasion. In this paper, the human laryngeal carcinoma epithelial cells (HEp-2) were used to investigate whether the reticulated iron cage could inhibit the infection of respiratory syncytial virus (RSV). Surface-modified DNA has a multivalent effect, which is expected to inhibit viral invasion by hybridization. Scanning electron microscopy (SEM) was used to confirm the formation of "iron cage" on the surface of cell membrane. The survival rate of the cells protected by the cage was increased from 24.1 to 4.4% to 49.0 (+ 10.0%). Immunofluorescence microscopy showed that the cage could inhibit virus invasion in two ways: steric hindrance hindered the binding of the virus to the cell membrane, decreased the flexibility of the cell membrane, inhibited the emergence of the virus, and inhibited the viral invasion. In this paper, nano-materials are used to achieve anti-virus invasion to a certain extent, which provides ideas for the development of new antiviral drugs and other new methods for the prevention and treatment of viral diseases.
2. Multifunctional Fe3O4@Au core-shell nanoflowers are targeted at cancer cells by dual-mode imaging and therapy. The development of multifunctional nanomaterials combining diagnosis and therapy is of great significance in the field of molecular medicine. High temperature can promote the rapid release of doxorubicin hydrochloride (Dox), a loaded anticancer drug, and produce red fluorescence. The release process can be monitored by confocal fluorescence microscopy. Targeted drug release. The Fe3O4@Au multifunctional nano-material combines fluorescence imaging with dual-mode MRI imaging to improve the diagnostic accuracy of cancer cells and facilitate monitoring drug release. The therapeutic effect achieved when the nano-material is loaded with 0.8 mu mDox is comparable to that achieved when 2.0 mu mDox is used alone. Therefore, chemotherapy and photothermal therapy are combined. In a word, this multifunctional nano-material has the function of targeting, dual-mode imaging and dual-therapy, which has potential significance for biomedical field, especially cancer treatment.
In summary, this paper has three innovations: (1) The SPR properties of metal nanoparticles can be effectively regulated by using biological molecules. (2) A virus defense system different from traditional small molecule design was constructed to form "iron cage" on the surface of the cell membrane to resist virus infection. (3) Targeted metal nanoparticles were prepared. This paper extends the application of metal nanoparticles in chemical and biosensor fields, provides a certain basis for further application of metal nanoparticles in cell imaging and photothermal therapy, and has a certain extent in cancer cell diagnosis and treatment. Clinical value.
【學(xué)位授予單位】：西南大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2013
【分類號】：R318.08;TB383.1
【共引文獻(xiàn)】
相關(guān)期刊論文 前10條
1 高征;白一鳴;吳強(qiáng);辛雅q ;何海洋;劉海;丁希宏;吳云召;王志斌;于曉琳;呂小穎;汪鼎民;陳諾夫;;納米顆粒表面等離激元在太陽電池中的應(yīng)用[J];微納電子技術(shù);2013年09期
2 王麗;桑宏慶;;核酸適體及其在食品安全領(lǐng)域的應(yīng)用[J];安徽科技學(xué)院學(xué)報;2013年05期
3 劉智明;鐘會清;郭周義;楊必文;;Conformation-dependent surface-enhanced Raman scattering of graphene oxide/metal nanoparticle hybrids[J];Chinese Optics Letters;2013年08期
4 董金超;溫桂清;劉慶業(yè);梁愛惠;蔣治良;;適配體修飾納米金催化共振瑞利散射光譜法測定血紅素[J];廣西師范大學(xué)學(xué)報(自然科學(xué)版);2013年03期
5 陳雯雯;郭永明;鄭問樞;鮮于運雷;王卓;蔣興宇;;金納米顆�？梢暬瘋鞲衅髟谏锓肿臃治鲋械难芯窟M(jìn)展[J];分析化學(xué);2014年03期
6 郝和群;姚萍;;葡聚糖分子量和接枝度對阿霉素/白蛋白-葡聚糖納米粒子體外抗腫瘤效果的影響[J];高等學(xué)�；瘜W(xué)學(xué)報;2014年03期
7 閆艷霞;姜利英;王芬芬;胡杰;岳保磊;;檢測三磷酸腺苷的交流阻抗型適體傳感器[J];微納電子技術(shù);2014年02期
8 姜利英;王芬芬;胡杰;岳保磊;閆艷霞;陳青華;;基于共面薄膜金電極的三磷酸腺苷適體傳感器[J];分析化學(xué);2014年05期
9 趙秋伶;劉玲玲;楊麗娜;張振宇;;基于DNA的比色分析法快速測定尿液中的Hg~(2+)[J];分析化學(xué);2014年05期
10 ;Cell-SELEX-based aptamer-conjugated nanomaterials for enhanced targeting of cancer cells[J];Science China(Chemistry);2011年08期
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1 沈松;Fenfen Kong;Xiaomeng Guo;Xinshi Wang;金一;;Biocompatible Fe_3O_4 nanoparticles with extremely low toxicity for photothermal therapy of cancer[A];第十一屆全國博士生學(xué)術(shù)年會（生物醫(yī)藥專題）論文集（中冊，，墻報P1-P24）[C];2013年
2 劉海;陳斌斌;王健;黃承志;;穩(wěn)定的金納米顆粒的催化活性研究[A];化學(xué)與創(chuàng)新藥物——2013年中國化學(xué)會產(chǎn)學(xué)研合作研討會會議論文集[C];2013年
3 Lu An;He Hu;Antao Dai;Yeming Zhuang;Hong Yang;Shiping Yang;;Multi-functional T_1 MR Imaging Contrast Agents as a Platform for Targeted Multi-modality Imaging[A];第八屆全國化學(xué)生物學(xué)學(xué)術(shù)會議論文摘要集[C];2013年
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1 Damra Elhaj Mustafa Abbass;金納米的制備、性能、標(biāo)記和催化應(yīng)用研究[D];華中師范大學(xué);2011年
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3 焦培福;抗體靶向多功能金納米粒子的設(shè)計、合成與生物活性研究[D];山東大學(xué);2012年
4 劉國棟;轉(zhuǎn)鐵蛋白修飾的載阿霉素氧化石墨烯納米�？鼓z質(zhì)瘤實驗研究[D];蘇州大學(xué);2013年
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8 楊辰;~(125)I-UdR-殼聚糖納米微粒的研制及其治療兔肝癌的研究[D];蘇州大學(xué);2013年
9 劉躍;銀和金納米顆粒的局域表面等離子體共振性質(zhì)及暗場光散射分析研究[D];西南大學(xué);2013年
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3 汪鳳林;功能型核苷酸用于光化學(xué)傳感器的研究[D];湖南大學(xué);2010年
4 張海杰;納米金為探針的朊蛋白檢測[D];西南大學(xué);2012年
5 盧文芬;雙氫青蒿素/聚乙二醇單甲醚—聚左旋乳酸嵌段共聚物膠束的制備及體內(nèi)外性質(zhì)研究[D];南方醫(yī)科大學(xué);2012年
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