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author:("Cui, daxing")
1.  Photosensitizer-Loaded Gold Vesicles with Strong Plasmonic Coupling Effect for Imaging-Guided Photothermal/Photodynamic Therapy 
ACS nano  2013;7(6):5320-5329.
A multifunctional theranostic platform based on photosensitizer-loaded plasmonic vesicular assemblies of gold nanoparticles (GNPs) is developed for effective cancer imaging and treatment. The gold vesicles (GVs) composed of a monolayer of assembled GNPs show strong absorbance in the near-infrared (NIR) range of 650–800 nm, as a result of the plasmonic coupling effect between neighboring GNPs in the vesicular membranes. The strong NIR absorption and the capability of encapsulating photosensitizer Ce6 in gold vesicles (GVs) enable tri-modality NIR fluorescence/thermal/photoacoustic imaging-guided synergistic photothermal/photodynamic therapy (PTT/PDT) with improved efficacy. The Ce6-loaded GVs (GV-Ce6) have the following characteristics: i) high Ce6 loading efficiency (up to ~18.4 wt%; ii) enhanced cellular uptake efficiency of Ce6; iii) simultaneous tri-modality NIR fluorescence/thermal/photoacoustic imaging; iv) synergistic PTT/PDT treatment with improved efficacy using single wavelength continuous wave laser irradiation.
doi:10.1021/nn4011686
PMCID: PMC3709863  PMID: 23721576
Gold vesicles; plasmonic coupling effect; photoacoustic imaging; photothermal therapy; photodynamic therapy; synergistic therapy
2.  Photosensitizer-Conjugated Silica-Coated Gold Nanoclusters for Fluorescence Imaging-Guided Photodynamic Therapy 
Biomaterials  2013;34(19):4643-4654.
Multifunctional theranostics have recently been intensively explored to optimize the efficacy and safety of therapeutic regimens. In this work, a photo-theranostic agent based on chlorin e6 (Ce6) photosensitizer-conjugated silica-coated gold nanoclusters (AuNCs@SiO2-Ce6) is strategically designed and prepared for fluorescence imaging-guided photodynamic therapy (PDT). The AuNCs@SiO2-Ce6 shows the following features: i) high Ce6 photosensitizer loading; ii) no non-specific release of Ce6 during its circulation; iii) significantly enhanced cellular uptake efficiency of Ce6, offering a remarkably improved photodynamic therapeutic efficacy compared to free Ce6; iv) subcellular characterization of the nanoformula via both the fluorescence of Ce6 and plasmon luminescence of AuNCs; v) fluorescence imaging-guided photodynamic therapy (PDT). This photo-theranostics owns good stability, high water dispersibility and solubility, non-cytotoxicity, and good biocompatibility, thus facilitating its biomedical applications, particularly for multi-modal optical, CT and photoacoustic (PA) imaging guided PDT or sonodynamic therapy.
doi:10.1016/j.biomaterials.2013.02.063
PMCID: PMC3645870  PMID: 23523428
Theranostics; silica; gold nanocluster; chlorin e6 (Ce6); fluorescence imaging; photodynamic therapy
3.  HAI-178 antibody-conjugated fluorescent magnetic nanoparticles for targeted imaging and simultaneous therapy of gastric cancer 
Nanoscale Research Letters  2014;9(1):274.
The successful development of safe and highly effective nanoprobes for targeted imaging and simultaneous therapy of in vivo gastric cancer is a great challenge. Herein we reported for the first time that anti-α-subunit of ATP synthase antibody, HAI-178 monoclonal antibody-conjugated fluorescent magnetic nanoparticles, was successfully used for targeted imaging and simultaneous therapy of in vivo gastric cancer. A total of 172 specimens of gastric cancer tissues were collected, and the expression of α-subunit of ATP synthase in gastric cancer tissues was investigated by immunohistochemistry method. Fluorescent magnetic nanoparticles were prepared and conjugated with HAI-178 monoclonal antibody, and the resultant HAI-178 antibody-conjugated fluorescent magnetic nanoparticles (HAI-178-FMNPs) were co-incubated with gastric cancer MGC803 cells and gastric mucous GES-1 cells. Gastric cancer-bearing nude mice models were established, were injected with prepared HAI-178-FMNPs via tail vein, and were imaged by magnetic resonance imaging and small animal fluorescent imaging system. The results showed that the α-subunit of ATP synthase exhibited high expression in 94.7% of the gastric cancer tissues. The prepared HAI-178-FMNPs could target actively MGC803 cells, realized fluorescent imaging and magnetic resonance imaging of in vivo gastric cancer, and actively inhibited growth of gastric cancer cells. In conclusion, HAI-178 antibody-conjugated fluorescent magnetic nanoparticles have a great potential in applications such as targeted imaging and simultaneous therapy of in vivo early gastric cancer cells in the near future.
doi:10.1186/1556-276X-9-274
PMCID: PMC4052287  PMID: 24948895
HAI-178 antibody; Fluorescent magnetic nanoparticles; Fluorescent imaging; Magnetic resonance imaging; Gastric cancer; Nude mice model
4.  RGD-conjugated silica-coated gold nanorods on the surface of carbon nanotubes for targeted photoacoustic imaging of gastric cancer 
Nanoscale Research Letters  2014;9(1):264.
Herein, we reported for the first time that RGD-conjugated silica-coated gold nanorods on the surface of multiwalled carbon nanotubes were successfully used for targeted photoacoustic imaging of in vivo gastric cancer cells. A simple strategy was used to attach covalently silica-coated gold nanorods (sGNRs) onto the surface of multiwalled carbon nanotubes (MWNTs) to fabricate a hybrid nanostructure. The cross-linked reaction occurred through the combination of carboxyl groups on the MWNTs and the amino group on the surface of sGNRs modified with a silane coupling agent. RGD peptides were conjugated with the sGNR/MWNT nanostructure; resultant RGD-conjugated sGNR/MWNT probes were investigated for their influences on viability of MGC803 and GES-1 cells. The nude mice models loaded with gastric cancer cells were prepared, the RGD-conjugated sGNR/MWNT probes were injected into gastric cancer-bearing nude mice models via the tail vein, and the nude mice were observed by an optoacoustic imaging system. Results showed that RGD-conjugated sGNR/MWNT probes showed good water solubility and low cellular toxicity, could target in vivo gastric cancer cells, and obtained strong photoacoustic imaging in the nude model. RGD-conjugated sGNR/MWNT probes will own great potential in applications such as targeted photoacoustic imaging and photothermal therapy in the near future.
doi:10.1186/1556-276X-9-264
PMCID: PMC4053550  PMID: 24948888
RGD peptide; Gold nanorods; Multiwalled carbon nanotubes; Optoacoustic imaging; Gastric cancer; Nude mice
5.  BRCAA1 antibody- and Her2 antibody-conjugated amphiphilic polymer engineered CdSe/ZnS quantum dots for targeted imaging of gastric cancer 
Nanoscale Research Letters  2014;9(1):244.
Successful development of safe and highly effective nanoprobes for targeted imaging of in vivo early gastric cancer is a great challenge. Herein, we choose the CdSe/ZnS (core-shell) quantum dots (QDs) as prototypical materials, synthesized one kind of a new amphiphilic polymer including dentate-like alkyl chains and multiple carboxyl groups, and then used the prepared amphiphilic polymer to modify QDs. The resultant amphiphilic polymer engineered QDs (PQDs) were conjugated with BRCAA1 and Her2 monoclonal antibody, and prepared BRCAA1 antibody- and Her2 antibody-conjugated QDs were used for in vitro MGC803 cell labeling and in vivo targeted imaging of gastric cancer cells. Results showed that the PQDs exhibited good water solubility, strong photoluminescence (PL) intensity, and good biocompatibility. BRCAA1 antibody- and Her2 antibody-conjugated QD nanoprobes successfully realized targeted imaging of in vivo gastric cancer MGC803 cells. In conclusion, BRCAA1 antibody- and Her2 antibody-conjugated PQDs have great potential in applications such as single cell labeling and in vivo tracking, and targeted imaging and therapeutic effects' evaluation of in vivo early gastric cancer cells in the near future.
doi:10.1186/1556-276X-9-244
PMCID: PMC4043660  PMID: 24940175
CdSe/ZnS quantum dots (QDs); Amphiphilic polymer; BRCAA1 antibody; Her2 antibody; Cytotoxicity; Targeted imaging; Gastric cancer cell
6.  Capillary-driven surface-enhanced Raman scattering (SERS)-based microfluidic chip for abrin detection 
Nanoscale Research Letters  2014;9(1):138.
Herein, we firstly demonstrate the design and the proof-of-concept use of a capillary-driven surface-enhanced Raman scattering (SERS)-based microfluidic chip for abrin detection. The micropillar array substrate was etched and coated with a gold film by microelectromechanical systems (MEMS) process to integrate into a lateral flow test strip. The detection of abrin solutions of various concentrations was performed by the as-prepared microfluidic chip. It was shown that the correlation between the abrin concentration and SERS signal was found to be linear within the range of 0.1 ng/mL to 1 μg/mL with a limit of detection of 0.1 ng/mL. Our microfluidic chip design enhanced the operability of SERS-based immunodiagnostic techniques, significantly reducing the complication and cost of preparation as compared to previous SERS-based works. Meanwhile, this design proved the superiority to conventional lateral flow test strips in respect of both sensitivity and quantitation and showed great potential in the diagnosis and treatment for abrin poisoning as well as on-site screening of abrin-spiked materials.
doi:10.1186/1556-276X-9-138
PMCID: PMC3994323  PMID: 24655483
Capillary force; Microfluidic chip; SERS; Abrin; Phytotoxin
7.  Carbon nanotubes as VEGF carriers to improve the early vascularization of porcine small intestinal submucosa in abdominal wall defect repair 
Insufficient early vascularization in biological meshes, resulting in limited host tissue incorporation, is thought to be the primary cause for the failure of abdominal wall defect repair after implantation. The sustained release of exogenous angiogenic factors from a biocompatible nanomaterial might be a way to overcome this limitation. In the study reported here, multiwalled carbon nanotubes (MWNT) were functionalized by plasma polymerization to deliver vascular endothelial growth factor165 (VEGF165). The novel VEGF165-controlled released system was incorporated into porcine small intestinal submucosa (PSIS) to construct a composite scaffold. Scaffolds incorporating varying amounts of VEGF165-loaded functionalized MWNT were characterized in vitro. At 5 weight percent MWNT, the scaffolds exhibited optimal properties and were implanted in rats to repair abdominal wall defects. PSIS scaffolds incorporating VEGF165-loaded MWNT (VEGF–MWNT–PSIS) contributed to early vascularization from 2–12 weeks postimplantation and obtained more effective collagen deposition and exhibited improved tensile strength at 24 weeks postimplantation compared to PSIS or PSIS scaffolds, incorporating MWNT without VEGF165 loading (MWNT–PSIS).
doi:10.2147/IJN.S58626
PMCID: PMC3956480  PMID: 24648727
vascular endothelial growth factor165; controlled release; multi-walled carbon nanotube; early vascularization
8.  A CCD-based reader combined with CdS quantum dot-labeled lateral flow strips for ultrasensitive quantitative detection of CagA 
Immunochromatographic assays are widely used to detect many analytes. CagA is proved to be associated closely with initiation of gastric carcinoma. Here, we reported that a charge-coupled device (CCD)-based test strip reader combined with CdS quantum dot-labeled lateral flow strips for quantitative detection of CagA was developed, which used 365-nm ultraviolet LED as the excitation light source, and captured the test strip images through an acquisition module. Then, the captured image was transferred to the computer and was processed by a software system. A revised weighted threshold histogram equalization (WTHE) image processing algorithm was applied to analyze the result. CdS quantum dot-labeled lateral flow strips for detection of CagA were prepared. One hundred sera samples from clinical patients with gastric cancer and healthy people were prepared for detection, which demonstrated that the device could realize rapid, stable, and point-of-care detection, with a sensitivity of 20 pg/mL.
doi:10.1186/1556-276X-9-57
PMCID: PMC3928623  PMID: 24495570
Test strip reader; CCD; Revised WTHE algorithm; CdS quantum dots; CagA
9.  Identification of Volatile Biomarkers of Gastric Cancer Cells and Ultrasensitive Electrochemical Detection based on Sensing Interface of Au-Ag Alloy coated MWCNTs 
Theranostics  2014;4(2):154-162.
Successful development of novel electrochemical biosensing interface for ultrasensitive detection of volatile biomarkers of gastric cancer cells is a challenging task. Herein we reported to screen out novel volatile biomarkers associated with gastric cancer cells and develop a novel Au-Ag alloy composites-coated MWCNTs as sensing interface for ultrasensitive detection of volatile biomarkers. MGC-803 gastric cancer cells and GES-1 gastric mucous cells were cultured in serum-free media. The sample preparation approaches and HS-SPME conditions were optimized for screening volatile biomarkers. Volatiles emitted from the headspace of the cells/medium culture were identified using GC-MS. The Au-Ag nanoparticles-coated multiwalled carbon nanotubes were prepared as a sensing interface for detection of volatile biomarkers. Results showed that eight different volatile metabolites were screened out between MGC-803 cells and GES-1 cells. Two compounds such as 3-octanone and butanone were specifically present in the headspace of the MGC-803 cells. Three volatiles such as 4-isopropoxybutanol, nonanol and 4-butoxy 1-butanol coexisted in the headspace of both the MGC-803 cells and the GES-1 cells, their concentrations in the headspace of the GES-1cells were markedly higher than those in the MGC-803 cells, three volatiles such as formic acid propyl ester, 1.4-butanediol and 2, 6, 11-trimethyl dodecane solely existed in the headspace of the GES-1 cells. The nanocomposites of MWNTs loaded with Au-Ag nanoparticles were prepared as a electrochemical sensing interface for detection of two volatile biomarkers, cyclic voltammetry studies showed that the fabricated sensor could detect 3-octanone in the range of 0~0.0025% (v/v) and with a detection limitation of 0.3 ppb, could detect butanone in the range of 0 ~ 0.055% (v/v), and with a detection limitation of 0.5 ppb, and exhibited good selectivity. The novel electrochemical biosensor combined with volatile biomarkers of gastric cancer owns great potential in applications such as early diagnosis and the prognosis of gastric cancer in near future.
doi:10.7150/thno.7560
PMCID: PMC3900800  PMID: 24465273
gastric cancer cells; volatile organic compounds; multi-wall carbon nanotubes; Au-Ag nanoparticles; cyclic voltammetry; electrochemical sensor.
10.  Shape-controllable synthesis of hydrophilic NaLuF4:Yb,Er nanocrystals by a surfactant-assistant two-phase system 
Nanoscale Research Letters  2013;8(1):518.
Water-soluble upconversion nanoparticles (UCNPs) were prepared by a one-pot procedure in a two-phase reacting system. Four kinds of surfactants were tested in the synthesis process as capping agent to tune size and morphology of nanocrystals. Nanoparticles (approximately 70 nm) and rods (400 nm and 2.5 μm) were synthesized, respectively. Then, Fourier transform infrared spectroscopy analysis confirmed the successful linking between UCNP surface and surfactant. Ionic liquids (ILs) and surfactants participated in synthesis process together, competing with each other to cap on UCNPs. ILs still led the competition of capping, while surfactants worked as cooperative assistants to develop functional surface. Further characterizations such as high-resolution transmission electron microscopy and X-ray diffraction indicated the changes in crystallization and phase transformation under the influence of surfactants. In addition, the growth mechanism of nanocrystals and upconversion fluorescence luminance was also investigated in detail. At last, the cytotoxicity of UCNPs was evaluated, which highly suggest that these surface-functionalized UCNPs are promising candidates for biomedical engineering.
doi:10.1186/1556-276X-8-518
PMCID: PMC4029583  PMID: 24314099
Upconversion; Rare earths; Surfactant; Capping agent; Luminescence; Cytotoxicity
11.  A Systematically Combined Genotype and Functional Combination Analysis of CYP2E1, CYP2D6, CYP2C9, CYP2C19 in Different Geographic Areas of Mainland China – A Basis for Personalized Therapy 
PLoS ONE  2013;8(10):e71934.
The cytochrome P450 is the major enzyme involved in drug metabolism. Single CYP genotypes and metabolic phenotypes have been widely studied, but no combination analysis has been conducted in the context of specific populations and geographical areas. This study is the first to systematically analyze the combined genotypes and functional combinations of 400 samples of major CYP genes—CYP2E1, CYP2D6, CYP2C9, and CYP2C19 in four geographical areas of mainland China. 167 different genotype combinations were identified, of which 25 had a greater than 1% frequency in the Chinese Han population. In addition, phenotypes of the four genes for each sample were in line with the predictions of previous studies of the four geographical areas. On the basis of the genotype classification, we were able to produce a systemic functional combinations analysis for the population. 25 of the combinations detected had at least two non-wild phenotypes and four showed a frequency above 1%. A bioinformatics analysis of the relationship between particular drugs and multi-genes was conducted. This is the first systematic study to analyze genotype combinations and functional combinations across whole Chinese population and could make a significant contribution in the field of personalized medicine and therapy.
doi:10.1371/journal.pone.0071934
PMCID: PMC3788764  PMID: 24098323
12.  Light-Triggered Theranostics Based on Photosensitizer-Conjugated Carbon Dots for Simultaneous Enhanced-Fluorescence Imaging and Photodynamic Therapy 
doi:10.1002/adma.201200650
PMCID: PMC3657566  PMID: 22718562
Theranostics; carbon dots; chlorin e6 (Ce6); fluorescence imaging; photodynamic therapy
13.  Carbon dots: a safe nanoscale substance for the immunologic system of mice 
Nanoscale Research Letters  2013;8(1):276.
We aimed at investigating the effect of carbon dots on the BALB/c mice immune system. Mice were respectively treated with different doses of carbon dots and saline. At 1 and 9 days after intravenous administration of carbon dots, splenocyte proliferation, subpopulation of the peripheral lymphocytes, and induction of primary immune responses in mice were investigated. The results showed that high dose of carbon dots could promote the percentages of CD3+ and interferon-γ (IFN-γ) secretion and decrease the proportions of CD4+/CD8+ on the first day after administration. At 9 days post exposure, the proliferation of splenocytes had a significant increase. IFN-γ secretion and proportions of CD3+/CD19+ were also found to have an obvious promotion, and both the percentages of CD4+ and CD8+ T lymphocytes were raised, whereas the expression of cytokines made little change in the treated groups, except for IL-12 which had a slight increase in the 50-mg/kg group. The weight coefficients and histological analysis of the spleen and thymus of the treated mice exerted fewer differences compared with those from the control mice. It suggests that carbon dots could influence the immune functions of normal BALB/c mice by inducing Th1 and Tc responses and that these effects were not enough to induce the morphological change of the immune organs.
doi:10.1186/1556-276X-8-276
PMCID: PMC3691753  PMID: 23758938
Carbon dots; Immune function; Splenocyte proliferation; Cytokine
14.  Folic acid-conjugated silica capped gold nanoclusters for targeted fluorescence/X-ray computed tomography imaging 
Background
Gastric cancer is 2th most common cancer in China, and is still the second most common cause of cancer-related death in the world. Successful development of safe and effective nanoprobes for in vivo gastric cancer targeting imaging is a big challenge. This study is aimed to develop folic acid (FA)-conjugated silica coated gold nanoclusters (AuNCs) for targeted dual-modal fluorescent and X-ray computed tomography imaging (CT) of in vivo gastric cancer cells.
Method
AuNCs were prepared, silica was coated on the surface of AuNCs, then folic acid was covalently anchored on the surface of AuNCs, resultant FA-conjugated AuNCs@SiO2 nanoprobes were investigated their cytotoxicity by MTT method, and their targeted ability to FR(+) MGC803 cells and FR(−) GES-1 cells. Nude mice model loaded with MGC803 cells were prepared, prepared nanoprobes were injected into nude mice via tail vein, and then were imaged by fluorescent and X-ray computed tomography (CT) imaging.
Results
FA-conjugated AuNCs@SiO2 nanoprobes exhibited good biocompatibility, and could target actively the FR(+) MGC-803 cells and in vivo gastric cancer tissues with 5 mm in diameter in nude mice models, exhibited excellent red emitting fluorescence imaging and CT imaging.
Conclusion
The high-performance FA-conjugated AuNCs@SiO2 nanoprobes can target in vivo gastric cancer cells, can be used for fluorescent and CT dual-mode imaging, and may own great potential in applications such as targeted dual-mode imaging of in vivo early gastric cancer and other tumors with FR positive expression in near future.
doi:10.1186/1477-3155-11-17
PMCID: PMC3669628  PMID: 23718865
Gold nanoclusters; Silica; Folic acid; Fluorescent imaging; X-ray computed tomography
15.  Metal ion-directed solution-phase tailoring: from large-area graphene oxide into nanoscale pieces 
Nanoscale Research Letters  2013;8(1):226.
Due to fascinating electronic properties and great potential in various applications, graphene has attracted great interest. Recently, much work have focused on the synthesis of different sizes and properties of graphene or graphene oxides (GOs), for example, graphene nanoribbons, nanosized graphene pieces, and nanosized triangular and hexagonal graphene sheets terminated by zigzag edges. Herein, we have demonstrated a widely available approach to fabricate the nanoscale GO pieces by directly solution-phase cutting a large-area GO sheet into nanoscale pieces via spontaneous redox reactions at room temperature. In this process, GO acts with dual functions as a model and a reducing reagent. With a typical example of silver ions, we have investigated in detail the influence of the reaction time and concentration of metal ions on yield and size of nanoscale GO pieces. Moreover, we also obtain Ag nanoparticle coating on the GO surface. Finally, a possible mechanism is suggested to explain the formation of nanoscale GO pieces.
doi:10.1186/1556-276X-8-226
PMCID: PMC3665674  PMID: 23672471
Graphene oxides; Nanoscale graphene oxide pieces; Spontaneous redox reaction; Metal particles
16.  Identification of 5-Iodotubercidin as a Genotoxic Drug with Anti-Cancer Potential 
PLoS ONE  2013;8(5):e62527.
Tumor suppressor p53, which is activated by various stress and oncogene activation, is a target for anti-cancer drug development. In this study, by screening panels of protein kinase inhibitors and protein phosphatase inhibitors, we identified 5-Iodotubercidin as a strong p53 activator. 5-Iodotubercidin is purine derivative and is used as an inhibitor for various kinases including adenosine kinase. We found that 5-Iodotubercidin could cause DNA damage, verified by induction of DNA breaks and nuclear foci positive for γH2AX and TopBP1, activation of Atm and Chk2, and S15 phosphorylation and up-regulation of p53. As such, 5-Iodotubercidin induces G2 cell cycle arrest in a p53-dependent manner. Itu also induces cell death in p53-dependent and -independent manners. DNA breaks were likely generated by incorporation of 5-Iodotubercidin metabolite into DNA. Moreover, 5-Iodotubercidin showed anti-tumor activity as it could reduce the tumor size in carcinoma xenograft mouse models in p53-dependent and -independent manners. These findings reveal 5-Iodotubercidin as a novel genotoxic drug that has chemotherapeutic potential.
doi:10.1371/journal.pone.0062527
PMCID: PMC3646850  PMID: 23667485
17.  Drug addiction is associated with leukocyte telomere length 
Scientific Reports  2013;3:1542.
Telomeres are protective chromosomal structures that play a key role in preserving genomic stability. Telomere length is known to be associated with ageing and age-related diseases. To study the impairment of telomeres induced by drug abuse, we conducted an association study in the Chinese Han population. Multivariate linear regression analyses were performed to evaluate the correlation of leukocyte telomere length (LTL) with addiction control status adjusted for age and gender. The results showed that drug abusers exhibited significantly shorter LTLs than controls (P = 1.32e−06). The time before relapse also presented an inverse correlation with LTL (P = 0.02). Drug abusers who had used heroin and diazepam displayed a shorter LTL than those taking other drugs (P = 0.018 and P = 0.009, respectively). Drug abusers who had ingested drugs via snuff exhibited longer LTLs than those using other methods (P = 0.02). These observations may offer a partial explanation for the effects of drug addiction on health.
doi:10.1038/srep01542
PMCID: PMC3607895  PMID: 23528991
18.  Systematic safety evaluation on photoluminescent carbon dots 
Nanoscale Research Letters  2013;8(1):122.
Photoluminescent carbon dots (C-dots) were prepared using the improved nitric acid oxidation method. The C-dots were characterized by tapping-mode atomic force microscopy, and UV–vis absorption spectroscopy. The C-dots were subjected to systematic safety evaluation via acute toxicity, subacute toxicity, and genotoxicity experiments (including mouse bone marrow micronuclear test and Salmonella typhimurium mutagenicity test). The results showed that the C-dots were successfully prepared with good stability, high dispersibility, and water solubility. At all studied C-dot dosages, no significant toxic effect, i.e., no abnormality or lesion, was observed in the organs of the animals. Therefore, the C-dots are non-toxic to mice under any dose and have potential use in fluorescence imaging in vivo, tumor cell tracking, and others.
doi:10.1186/1556-276X-8-122
PMCID: PMC3602655  PMID: 23497260
Carbon dots; Biocompatibility; Toxicity
19.  Rapid screening and identification of dominant B cell epitopes of HBV surface antigen by quantum dot-based fluorescence polarization assay 
Nanoscale Research Letters  2013;8(1):118.
A method for quickly screening and identifying dominant B cell epitopes was developed using hepatitis B virus (HBV) surface antigen as a target. Eleven amino acid fragments from HBV surface antigen were synthesized by 9-fluorenylmethoxy carbonyl solid-phase peptide synthesis strategy, and then CdTe quantum dots were used to label the N-terminals of all peptides. After optimizing the factors for fluorescence polarization (FP) immunoassay, the antigenicities of synthetic peptides were determined by analyzing the recognition and combination of peptides and standard antibody samples. The results of FP assays confirmed that 10 of 11 synthetic peptides have distinct antigenicities. In order to screen dominant antigenic peptides, the FP assays were carried out to investigate the antibodies against the 10 synthetic peptides of HBV surface antigen respectively in 159 samples of anti-HBV surface antigen-positive antiserum. The results showed that 3 of the 10 antigenic peptides may be immunodominant because the antibodies against them existed more widely among the samples and their antibody titers were higher than those of other peptides. Using three dominant antigenic peptides, 293 serum samples were detected for HBV infection by FP assays; the results showed that the antibody-positive ratio was 51.9% and the sensitivity and specificity were 84.3% and 98.2%, respectively. In conclusion, a quantum dot-based FP assay is a very simple, rapid, and convenient method for determining immunodominant antigenic peptides and has great potential in applications such as epitope mapping, vaccine designing, or clinical disease diagnosis in the future.
doi:10.1186/1556-276X-8-118
PMCID: PMC3605173  PMID: 23452727
Dominant epitope; Quantum dots; Antigenic peptide; Fluorescence polarization; HBV; Surface antigen
20.  Phase and Size Controllable Synthesis of NaYbF4 Nanocrystals in Oleic Acid/ Ionic Liquid Two-Phase System for Targeted Fluorescent Imaging of Gastric Cancer 
Theranostics  2013;3(3):210-222.
Upconversion nanocrystals with small size and strong fluorescent signals own great potential in applications such as biomolecule-labeling, in vivo tracking and molecular imaging. Herein we reported that NaYbF4: 25%Gd, 2%Tm upconversion nanocrystals with small size and strong fluorescent signals were controllably synthesized by oleic acid (OA)/ ionic liquid (IL) two-phase system for targeted fluorescent imaging of gastric cancer in vivo. The optimal synthesis condition of NaYbF4: 25%Gd, 2%Tm upconversion nanocrystals by OA/IL two-phase system was established, adding more metal ion such as Na+ ion could facilitate the size control and crystal-phase transition, more importantly, markedly enhancing fluorescent intensity of beta-phase nanocrystals compared with traditional methods. Alpha-phase NaYbF4, 2%Tm upconversion nanocrystals with less than 10nm in diameter and beta-phase NaYbF4: 25%Gd, 2%Tm upconversion nanocrystals with 30 nm or so in diameter and strong fluorescent signals were obtained, these synthesized nanocrystals exhibited very low cytotoxicity. Folic acid-conjugated silica-modified beta-phase NaYbF4: 25%Gd, 2%Tm upconversion nanocrystals were prepared, could actively target gastric cancer tissues implanted into nude mice in vivo, and realized targeted fluorescent imaging. Folic acid-conjugated silica-modified NaYbF4: 25%Gd, 2%Tm upconversion nanocrystals show great potential in applications such as targeted near infared radiation fluorescent imaging, magnetic resonance imaging and targeted therapy of gastric cancer in the near future.
doi:10.7150/thno.5298
PMCID: PMC3590590  PMID: 23471455
NaYbF4: 25%Gd; 2%Tm upconversion nanocrystals; synthesis; targeted imaging; fluorescent imaging; gastric cancer; cytotoxicity.
21.  Toxicity Assessments of Near-infrared Upconversion Luminescent LaF3:Yb,Er in Early Development of Zebrafish Embryos 
Theranostics  2013;3(4):258-266.
This study reports the effects of upconversion nanoparticles (UCNPs) LaF3:Yb,Er on zebrafish, with the aim of investigating UCNPs toxicity. LaF3:Yb,Er were prepared by an oleic acid/ionic liquid two-phase system, and characterized by transmission electron microscope and X-ray powder diffraction. 140 zebrafish embryos were divided into six test groups and one control group, and respectively were injected into 5, 25, 50, 100, 200, 400 μg/mL LaF3:Yb,Er@SiO2 solution, and respectively were raised for 5 days. Each experiment was repeated ten times. Results showed that water-soluble LaF3:Yb,Er were successfully prepared, and did not exhibit obvious toxicity to zebrafish embryos under 100 μg/mL, but exhibited chronic toxicities 200 μg/mL in vivo, resulting in malformations and delayed hatching rate and embryonic and larval development. The excretion channels of LaF3:Yb,Er in adult zebrafish were mainly found in the intestine after being injected evenly for 24 h. In conclusion, the exploration of LaF3:Yb,Er for in vivo applications in animals and humans must consider UCNPs biocompatibility.
doi:10.7150/thno.5701
PMCID: PMC3630526  PMID: 23606912
Upconversion nanoparticles (UCNPs); biocompatibility; toxicity; zebrafish embryo.
22.  Establishment of a method to determine the magnetic particles in mouse tissues 
Nanoscale Research Letters  2012;7(1):665.
This work is aimed to evaluate a method to detect the residual magnetic nanoparticles (MNPs) in animal tissues. Ferric ions released from MNPs through acidification with hydrochloric acid can be measured by complexation with potassium thiocyanate. MNPs in saline could be well detected by this chemical colorimetric method, whereas the detected sensitivity decreased significantly when MNPs were mixed with mouse tissue homogenates. In order to check the MNPs in animal tissues accurately, three improvements have been made. Firstly, proteinase K was used to digest the proteins that might bind with iron, and secondly, ferrosoferric oxide (Fe3O4) was collected by a magnetic field which could capture MNPs and leave the bio-iron in the supernatant. Finally, the collected MNPs were carbonized in the muffle furnace at 420°C before acidification to ruin the groups that might bind with ferric ions such as porphyrin. Using this method, MNPs in animal tissues could be well measured while avoiding the disturbance of endogenous iron and iron-binding groups.
doi:10.1186/1556-276X-7-665
PMCID: PMC3552763  PMID: 23216680
Ferric ions; Magnetic nanoparticles; Potassium thiocyanate; Mouse tissue; Chemical colorimetric method
23.  Differential Expression of Phospholipase C Epsilon 1 Is Associated with Chronic Atrophic Gastritis and Gastric Cancer 
PLoS ONE  2012;7(10):e47563.
Background
Chronic inflammation plays a causal role in gastric tumor initiation. The identification of predictive biomarkers from gastric inflammation to tumorigenesis will help us to distinguish gastric cancer from atrophic gastritis and establish the diagnosis of early-stage gastric cancer. Phospholipase C epsilon 1 (PLCε1) is reported to play a vital role in inflammation and tumorigenesis. This study was aimed to investigate the clinical significance of PLCε1 in the initiation and progression of gastric cancer.
Methodology/Principal Findings
Firstly, the mRNA and protein expression of PLCε1 were analyzed by reverse transcription-PCR and Western blotting in normal gastric mucous epithelial cell line GES-1 and gastric cancer cell lines AGS, SGC7901, and MGC803. The results showed both mRNA and protein levels of PLCε1 were up-regulated in gastric cancer cells compared with normal gastric mucous epithelial cells. Secondly, this result was confirmed by immunohistochemical detection in a tissue microarray including 74 paired gastric cancer and adjacent normal tissues. Thirdly, an independence immunohistochemical analysis of 799 chronic atrophic gastritis tissue specimens demonstrated that PLCε1 expression in atrophic gastritis tissues were down-regulated since PLCε1 expression was negative in 524 (65.6%) atrophic gastritis. In addition, matched clinical tissues from atrophic severe gastritis and gastric cancer patients were used to further confirm the previous results by analyzing mRNA and protein levels expression of PLCε1 in clinical samples.
Conclusions/Significances
Our results suggested that PLCε1 protein may be a potential biomarker to distinguish gastric cancer from inflammation lesion, and could have great potential in applications such as diagnosis and pre-warning of early-stage gastric cancer.
doi:10.1371/journal.pone.0047563
PMCID: PMC3471869  PMID: 23077637
24.  Chloroplasts-mediated biosynthesis of nanoscale Au-Ag alloy for 2-butanone assay based on electrochemical sensor 
Nanoscale Research Letters  2012;7(1):475.
We reported a one-pot, environmentally friendly method for biosynthesizing nanoscale Au-Ag alloy using chloroplasts as reducers and stabilizers. The prepared nanoscale Au-Ag alloy was characterized by UV–visible spectroscopy, X-ray diffraction (XRD) and high resolution transmission electron microscopy (HR-TEM). Fourier transform infrared spectroscopy (FTIR) analysis was further used to identify the possible biomolecules from chloroplasts that are responsible for the formation and stabilization of Au-Ag alloy. The FTIR results showed that chloroplast proteins bound to the nanoscale Au-Ag alloy through free amino groups. The bimetallic Au-Ag nanoparticles have only one plasmon band, indicating the formation of an alloy structure. HR-TEM images showed that the prepared Au-Ag alloy was spherical and 15 to 20 nm in diameter. The high crystallinity of the Au-Ag alloy was confirmed by SAED and XRD patterns. The prepared Au-Ag alloy was dispersed into multiwalled carbon nanotubes (MWNTs) to form a nanosensing film. The nanosensing film exhibited high electrocatalytic activity for 2-butanone oxidation at room temperature. The anodic peak current (Ip) has a linear relationship with the concentrations of 2-butanone over the range of 0.01% to 0.075% (v/v), when analyzed by cyclic voltammetry. The excellent electronic catalytic characteristics might be attributed to the synergistic electron transfer effects of Au-Ag alloy and MWNTs. It can reasonably be expected that this electrochemical biosensor provided a promising platform for developing a breath sensor to screen and pre-warn of early cancer, especially gastric cancer.
doi:10.1186/1556-276X-7-475
PMCID: PMC3506472  PMID: 22916797
Chloroplasts; Au-Ag alloy; Nanosensing film
25.  Enhanced bioavailability and efficiency of curcumin for the treatment of asthma by its formulation in solid lipid nanoparticles 
Curcumin has shown considerable pharmacological activity, including anti-inflammatory, but its poor bioavailability and rapid metabolization have limited its application. The purpose of the present study was to formulate curcumin-solid lipid nanoparticles (curcumin-SLNs) to improve its therapeutic efficacy in an ovalbumin (OVA)-induced allergic rat model of asthma. A solvent injection method was used to prepare the curcumin-SLNs. Physiochemical properties of curcumin-SLNs were characterized, and release experiments were performed in vitro. The pharmacokinetics in tissue distribution was studied in mice, and the therapeutic effect of the formulation was evaluated in the model. The prepared formulation showed an average size of 190 nm with a zeta potential value of −20.7 mV and 75% drug entrapment efficiency. X-ray diffraction analysis revealed the amorphous nature of the encapsulated curcumin. The release profile of curcumin-SLNs was an initial burst followed by sustained release. The curcumin concentrations in plasma suspension were significantly higher than those obtained with curcumin alone. Following administration of the curcumin-SLNs, all the tissue concentrations of curcumin increased, especially in lung and liver. In the animal model of asthma, curcumin-SLNs effectively suppressed airway hyperresponsiveness and inflammatory cell infiltration and also significantly inhibited the expression of T-helper-2-type cytokines, such as interleukin-4 and interleukin-13, in bronchoalveolar lavage fluid compared to the asthma group and curcumin-treated group. These observations implied that curcumin-SLNs could be a promising candidate for asthma therapy.
doi:10.2147/IJN.S30428
PMCID: PMC3414206  PMID: 22888226
airway hyperresponsiveness; pharmacokinetics; curcumin; solid lipid nanoparticles

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