- Email: [email protected]
Highly specific electrochemical sensor of tumor marker using multi-nanoparticle labeling based 3D origami paper analytical device
ChinaNanomedicine Abstracts / Nanomedicine: Nanotechnology, Biology, and Medicine 12 (2016) 449–575
important role in the early staging diagnosis of tumors. Here we report the design and synthesis of a fluorescent off–on nanoprobe for MMP families (for an instance, collagenase IV, including MMP2, MMP4, and MMP9). The fabricated fluorescent nano-switch is the fluorescein isothiocyanate (FITC)-attached gold nanoparticle (GNP). The spacer inserted between FITC and GNP is a small peptide containing the core substrate sequence of MMPs and a free thiol group on the terminal cysteine. To ensure the desirable solubility, stability, and in vivo circulation of nano-switch, thiolated polyethylene glycol monomethyl ether (HS-mPEG2000) was also conjugated to the surface of GNP. The structure of the nano-switch was optimized through adjusting the molar ratio of GNP vs. p-FITC, investigating the effect on the addition of HS-mPEG2000, and evaluating fluorescence recovery efficiency of the nano-switch. Investigated using confocal laser fluorescence microscope technology, the cellular uptake result showed that with the help of GNPs, the nano-switch can be more easily in taken by HepG2 cells (liver hepatocellular carcinoma) and lighten the green fluorescence of FITC around GNPs inside cells. However, the green fluorescence was only found in the cell culture medium for the p-FITC group. Furthermore, tissue frozen section results demonstrated that (1) the nano-switch showed higher fluorescence intensity in tumor tissues; (2) the fluorescence recovery of the nano-switch was not only found in the margin but also in the center of tumor tissues; (3) the nano-switch exhibited lower distribution in normal tissues including heart, spleen, and lung; and (4) when comparing with p-FITC, the similar and higher accumulation of the nano-switch in liver and kidney, respectively, indicated its liver targeting and renal elimination characters. http://dx.doi.org/10.1016/j.nano.2015.12.182
High yield luminescent N-doped carbon nanodots derived from nitrogen-containing biomass for bioimaging Lei Wanga, Baoqiang Lia,⁎, Li Lib, Daqing Weia, Yujie Fenga, Dechang Jiaa, a Institute for Advanced Ceramics and State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin, China, b School of Life Science and Technology, Harbin Institute of Technology, Harbin, China ⁎Corresponding author. E-mail address: [email protected] (B. Li) Luminescent carbon nanodots-based (CNDs) imaging probes are expected to generate new medical diagnostic tools based on their superior brightness, photostability and non-toxicity compared with conventional fluorescent semiconductor probes.1 Nitrogen Doping of CNDs has been considered as the most promising way to improve fluorescence quantum yield (QY) of CNDs, which is extremely important both fundamentally and technologically. Yang et al reported luminescent N-doped CNDs (N-CNDs) derived from citric acid and ethylenediamine with high QY (80%). However the yield of N-CNDs was as low as 7.8%, which challenged the wide application of N-CNDs served as medical diagnostic probes. Here high yield (38.4%) N-CNDs with QY of 35% derived from low cost N-containing biomass (chitosan) were prepared by hydrothermal carbonization. A generally broad photoluminescence spectrum (380-550 nm) was shown in Figure 1, A with the phenomenon of λex-dependent λem ascribed to the defect sites on the surface of N-CNDs. The XPS N1s peaks of N-CNDs at 399.7 and 401.6 eV were corresponding to –NH2 and C–N–C groups (Figure 1, B), which indicated that amino groups in chitosan biomass was mainly remained after carbonization. The morphology of N-CNDs was uniform and monodisperse with an average diameter of 4.8 ± 0.8 nm (Figure 1, C). As shown in Figure 1, D, the green fluorescence can be observed in the liver and digestive system of zebra fishes after 3 h of incubation with the N-CNDs, which means that the bioimaging probe can be easily uptaken by zebrafishes from water. A high yield N-CNDs from low cost N-containing biomass served as nontoxic labels for imaging in vivo.
The project was sponsored by NSFC: 51372051, 51321061, 2012CB3393, 2013TS09, 2013RFLXJ023 and HIT.IBRSEM.201302.
511
Figure 1. The PL spectrum (A), XPS N1s (B) and TEM (C) of N-CNDs. Fluorescence microscopy images for zebra fish larvae (F).
http://dx.doi.org/10.1016/j.nano.2015.12.183
Highly specific electrochemical sensor of tumor marker using multi-nanoparticle labeling based 3D origami paper analytical device Shenguang Ge, Mei Yan, Jinghua Yu⁎, School of Chemistry and Chemical Engineering, University of Jinan, Jinan, China ⁎Corresponding author. E-mail address: [email protected] (J. Yu) A simple, low-cost, and sensitive 3D origami paper electrochemical sensor device was developed based on a novel gold nanoparticle modified porous paper working electrode and multi-nanoparticle labeling for point-of-care diagnosis. Paper device was designed on a computer and then printed on chromatographic paper using a commercially available office printer. The three electrode system (working electrode, reference electrode, and counter electrode) was prepared on the paper device through screen-printed technique. As shown in Scheme 1, a novel porous Au-paper working electrode was developed on a compatibly designed origami electrochemical device through the growth of an interconnected Au nanoparticles layer on the surfaces of cellulose fibers in the paper sample zone to enhance the conductivity of the paper sample zone. Next, three capture antibodies were immobilized at sample zone, and then the paper was folded. The nanoparticle-based, multi-marker approach exploited the direct electrochemical oxidation of metal nanoparticles (MNPs) to report on the presence of markers. We selected Cu, Ag and Pd metal nanoparticles functionalized with electrostatically bound corresponding antibodies CA 153, CEA and HCG as the labeling for the determination of breast cancer. With sandwich-type immunoassay format, these MNP-antibody conjugates were incubated with antigen captured by capture antibody on the electrode array. Electrochemical scans then oxidized the attached MNPs directly, with different levels of current corresponding to the concentration of antigen present on the sensor. Three oxidation peaks at +300, +450 and +950 mV versus Ag/AgCl corresponding to the oxidation of Cu, Ag and Pd were detected. The electrochemical signal increased linearly with the logarithm of tumor markers concentrations in the range from 1.0 U mL− 1 to 100 U mL− 1, from 0.1 mg mL− 1 to 5.0 mg mL− 1, and from 0.2 mIU mL− 1 to 10 mIU mL− 1, respectively. The limits of detection at a signal-tonoise ratio of 3 for the three tumor markers were 0.3 U mL− 1, 0.04 mg mL− 1, and 0.07 mIU mL− 1, respectively.
Scheme 1. Schematic of 3D origami paper electrochemical sensor device and determination.
http://dx.doi.org/10.1016/j.nano.2015.12.184
important role in the early staging diagnosis of tumors. Here we report the design and synthesis of a fluorescent off–on nanoprobe for MMP families (for an instance, collagenase IV, including MMP2, MMP4, and MMP9). The fabricated fluorescent nano-switch is the fluorescein isothiocyanate (FITC)-attached gold nanoparticle (GNP). The spacer inserted between FITC and GNP is a small peptide containing the core substrate sequence of MMPs and a free thiol group on the terminal cysteine. To ensure the desirable solubility, stability, and in vivo circulation of nano-switch, thiolated polyethylene glycol monomethyl ether (HS-mPEG2000) was also conjugated to the surface of GNP. The structure of the nano-switch was optimized through adjusting the molar ratio of GNP vs. p-FITC, investigating the effect on the addition of HS-mPEG2000, and evaluating fluorescence recovery efficiency of the nano-switch. Investigated using confocal laser fluorescence microscope technology, the cellular uptake result showed that with the help of GNPs, the nano-switch can be more easily in taken by HepG2 cells (liver hepatocellular carcinoma) and lighten the green fluorescence of FITC around GNPs inside cells. However, the green fluorescence was only found in the cell culture medium for the p-FITC group. Furthermore, tissue frozen section results demonstrated that (1) the nano-switch showed higher fluorescence intensity in tumor tissues; (2) the fluorescence recovery of the nano-switch was not only found in the margin but also in the center of tumor tissues; (3) the nano-switch exhibited lower distribution in normal tissues including heart, spleen, and lung; and (4) when comparing with p-FITC, the similar and higher accumulation of the nano-switch in liver and kidney, respectively, indicated its liver targeting and renal elimination characters. http://dx.doi.org/10.1016/j.nano.2015.12.182
High yield luminescent N-doped carbon nanodots derived from nitrogen-containing biomass for bioimaging Lei Wanga, Baoqiang Lia,⁎, Li Lib, Daqing Weia, Yujie Fenga, Dechang Jiaa, a Institute for Advanced Ceramics and State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin, China, b School of Life Science and Technology, Harbin Institute of Technology, Harbin, China ⁎Corresponding author. E-mail address: [email protected] (B. Li) Luminescent carbon nanodots-based (CNDs) imaging probes are expected to generate new medical diagnostic tools based on their superior brightness, photostability and non-toxicity compared with conventional fluorescent semiconductor probes.1 Nitrogen Doping of CNDs has been considered as the most promising way to improve fluorescence quantum yield (QY) of CNDs, which is extremely important both fundamentally and technologically. Yang et al reported luminescent N-doped CNDs (N-CNDs) derived from citric acid and ethylenediamine with high QY (80%). However the yield of N-CNDs was as low as 7.8%, which challenged the wide application of N-CNDs served as medical diagnostic probes. Here high yield (38.4%) N-CNDs with QY of 35% derived from low cost N-containing biomass (chitosan) were prepared by hydrothermal carbonization. A generally broad photoluminescence spectrum (380-550 nm) was shown in Figure 1, A with the phenomenon of λex-dependent λem ascribed to the defect sites on the surface of N-CNDs. The XPS N1s peaks of N-CNDs at 399.7 and 401.6 eV were corresponding to –NH2 and C–N–C groups (Figure 1, B), which indicated that amino groups in chitosan biomass was mainly remained after carbonization. The morphology of N-CNDs was uniform and monodisperse with an average diameter of 4.8 ± 0.8 nm (Figure 1, C). As shown in Figure 1, D, the green fluorescence can be observed in the liver and digestive system of zebra fishes after 3 h of incubation with the N-CNDs, which means that the bioimaging probe can be easily uptaken by zebrafishes from water. A high yield N-CNDs from low cost N-containing biomass served as nontoxic labels for imaging in vivo.
The project was sponsored by NSFC: 51372051, 51321061, 2012CB3393, 2013TS09, 2013RFLXJ023 and HIT.IBRSEM.201302.
511
Figure 1. The PL spectrum (A), XPS N1s (B) and TEM (C) of N-CNDs. Fluorescence microscopy images for zebra fish larvae (F).
http://dx.doi.org/10.1016/j.nano.2015.12.183
Highly specific electrochemical sensor of tumor marker using multi-nanoparticle labeling based 3D origami paper analytical device Shenguang Ge, Mei Yan, Jinghua Yu⁎, School of Chemistry and Chemical Engineering, University of Jinan, Jinan, China ⁎Corresponding author. E-mail address: [email protected] (J. Yu) A simple, low-cost, and sensitive 3D origami paper electrochemical sensor device was developed based on a novel gold nanoparticle modified porous paper working electrode and multi-nanoparticle labeling for point-of-care diagnosis. Paper device was designed on a computer and then printed on chromatographic paper using a commercially available office printer. The three electrode system (working electrode, reference electrode, and counter electrode) was prepared on the paper device through screen-printed technique. As shown in Scheme 1, a novel porous Au-paper working electrode was developed on a compatibly designed origami electrochemical device through the growth of an interconnected Au nanoparticles layer on the surfaces of cellulose fibers in the paper sample zone to enhance the conductivity of the paper sample zone. Next, three capture antibodies were immobilized at sample zone, and then the paper was folded. The nanoparticle-based, multi-marker approach exploited the direct electrochemical oxidation of metal nanoparticles (MNPs) to report on the presence of markers. We selected Cu, Ag and Pd metal nanoparticles functionalized with electrostatically bound corresponding antibodies CA 153, CEA and HCG as the labeling for the determination of breast cancer. With sandwich-type immunoassay format, these MNP-antibody conjugates were incubated with antigen captured by capture antibody on the electrode array. Electrochemical scans then oxidized the attached MNPs directly, with different levels of current corresponding to the concentration of antigen present on the sensor. Three oxidation peaks at +300, +450 and +950 mV versus Ag/AgCl corresponding to the oxidation of Cu, Ag and Pd were detected. The electrochemical signal increased linearly with the logarithm of tumor markers concentrations in the range from 1.0 U mL− 1 to 100 U mL− 1, from 0.1 mg mL− 1 to 5.0 mg mL− 1, and from 0.2 mIU mL− 1 to 10 mIU mL− 1, respectively. The limits of detection at a signal-tonoise ratio of 3 for the three tumor markers were 0.3 U mL− 1, 0.04 mg mL− 1, and 0.07 mIU mL− 1, respectively.
Scheme 1. Schematic of 3D origami paper electrochemical sensor device and determination.
http://dx.doi.org/10.1016/j.nano.2015.12.184