Aptamer-based biosensors and application in tumor theranostics.

An aptamer is a short oligonucleotide chain that can specifically recognize targeting analytes. Due to its high specificity, low cost, and good biocompatibility, aptamers as the targeting elements of biosensors have been applied widely in non-invasive tumor imaging and treatment in situ to replace traditional methods. In this review, we will summarize recent advances in using aptamer-based biosensors in tumor diagnosis. After a brief introduction of the advantage of aptamers compared with enzyme sensors and immune sensors, the different sensing designs and mechanisms based on 3 signal transduction modes will be reviewed to cover different kinds of analytical methods, including: electrochemistry analysis, colorimetry analysis, and fluorescence analysis. Finally, the prospective advantages of aptamer-based biosensors in tumor theranostics and post-treatment monitoring are also evaluated in this review.

Inactivated Covid-19 vaccine did not undermine live birth and neonatal outcomes of women with frozen-thawed embryo transfer.

STUDY QUESTION: Does inoculation with inactivated vaccines against coronavirus disease 2019 (Covid-19) before frozen-thawed embryo transfer (FET) affect live birth and neonatal outcomes? SUMMARY ANSWER: Inactivated Covid-19 vaccines did not undermine live birth and neonatal outcomes of women planning for FET. WHAT IS KNOWN ALREADY: Accumulating reports are now available indicating the safe use of mRNA vaccines against Covid-19 in pregnant and lactating women, and a few reports indicate that they are not associated with adverse effects on ovarian stimulation or early pregnancy outcomes following IVF. Evidence about the safety of inactivated Covid-19 vaccines is very limited. STUDY DESIGN, SIZE, DURATION: This is a retrospective cohort analysis from Reproductive Medical Center of a tertiary teaching hospital. Clinical records and vaccination record of 2574 couples with embryos transferred between 1 March 2021 and 30 September 2021 were screened for eligibility of this study. PARTICIPANTS/MATERIALS, SETTING, METHODS: Clinical and vaccination data of infertile couples planning for FET were screened for eligibility of the study. The reproductive and neonatal outcomes of FET women inoculated with inactivated Covid-19 vaccines or not were compared. The primary outcomes were live birth rate per embryo transfer cycle and newborns' birth height and weight. Secondary outcomes included rates of ongoing pregnancy, clinical pregnancy, biochemical pregnancy and spontaneous miscarriage. Multivariate logistical regression and propensity score matching (PSM) analyses were performed to minimize the influence of confounding factors. Subgroup analyses, including single dose versus double dose of the vaccines and the time intervals between the first vaccination and embryo transfer, were also performed. MAIN RESULTS AND THE ROLE OF CHANCE: Vaccinated women have comparable live birth rates (43.6% versus 45.0% before PSM, P = 0.590; and 42.9% versus 43.9% after PSM, P = 0.688), ongoing pregnancy rates (48.2% versus 48.1% before PSM, P = 0.980; and 52.2% versus 52.7% after PSM, P = 0.875) and clinical pregnancy rate (55.0% versus 54.8% before PSM, P = 0.928; and 54.7% versus 54.2% after PSM, P = 0.868) when compared with unvaccinated counterparts. The newborns' birth length (50.0 ± 1.6 versus 49.0 ± 2.9 cm before PSM, P = 0.116; and 49.9 ± 1.7 versus 49.3 ± 2.6 cm after PSM, P = 0.141) and birth weight (3111.2 ± 349.9 versus 3030.3 ± 588.5 g before PSM, P = 0.544; and 3053.8 ± 372.5 versus 3039.2 ± 496.8 g after PSM, P = 0.347) were all similar between the two groups. Neither single dose nor double dose of vaccines, as well as different intervals between vaccination and embryo transfer showed any significant impacts on reproductive and neonatal outcomes. LIMITATIONS, REASONS FOR CAUTION: The main findings might be limited by retrospective design. Besides, inoculations of triple dose of Covid-19 vaccines were not available by the time of data collection, thus the results cannot reflect the safe use of triple dose of inactivated Covid-19 vaccines. Finally, history of Covid-19 infection was based on patients' self-report rather than objective laboratory tests. WIDER IMPLICATIONS OF THE FINDINGS: Eligible individuals of inactivated vaccines against Covid-19 should not postpone vaccination plan because of their embryo transfer schedule, or vice versa. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Medical Key Discipline of Guangzhou (2021-2023). All authors had nothing to disclose. TRIAL REGISTRATION NUMBER: N/A.

Exploring the multidimensional relationships between social media support, social confidence, perceived media credibility and life attitude during the COVID-19 pandemic.

Previous literature mainly focuses on the impact of social media support on social trust, emotional effect and life attitude, and affirmed the social governance value of social media support. However, the multidimensional relationship between social media support and social confidence, perceived media credibility and life attitude during the COVID-19 pandemic is an important, yet less explored, research issue. The present research aimed to fill in this gap by a survey of 1343 participants who are permanent residents aged 18 and above in a city through WeChat social networking platform. The results showed that: (1) social media support exerted direct influence on social confidence, perceived media credibility and life attitude; (2) perceived media credibility positively influenced social confidence; (3) social media support not only directly promoted social confidence, but also indirectly influenced social confidence through public's perceived media credibility. These findings suggested that strengthening social media support during the COVID-19 pandemic is not only helpful to reconstitute the public's confidence in prevailing against the pandemic, but also is able to help promote the diversification of the power of public network autonomy. This study highlighted social media support as an effective path to improve the ability of social governance.

A novel label-free terbium(iii)-aptamer based aptasensor for ultrasensitive and highly specific detection of acute lymphoma leukemia cells.

Acute leukemia is a malignant clonal disease of hematopoietic stem cells with a high prevalence and mortality rate. However, there are no efficient tools to facilitate early diagnosis and treatment of leukemia. Therefore, development of new methods for the early diagnosis and prevention of leukemia, especially non-invasive diagnosis at the cellular level, is imperative. Here, a label-free signal-on fluorescence aptasensor based on terbium(iii)-aptamer (Tb3+-apt) was applied for the detection of leukemia. The aptamer sensitizes the fluorescence of Tb3+ and forms the strong fluorescent Tb3+-apt probe. The target cells, the T-cell acute lymphoblastic leukemia cell line (CCRF-CEM) combined with the Tb3+-apt probe to form the Tb3+-apt-CEM complex, were removed by centrifugation, and the supernatant containing a small amount of the Tb3+-apt probe was detected using a fluorescence spectrophotometer. The logarithm of cell concentration showed a good linear relationship (R2 = 0.9881) with the fluorescence signal. The linear range for CCRF-CEM detection was 5-5 × 106 cells per ml, while the detection limit was 5 cells per ml of the binding buffer. Clinical samples were collected from 100 cases, and the specificity and positive rates detected by this method were up to 94% and 90%, respectively. Therefore, a single-stranded DNA-sensitized terbium(iii) luminescence method diagnostic was developed which is rapid, sensitive, and economical and can be used for diagnosis of various types of leukemia at the early stage.

Label-Free and Sensitive Detection of Thrombomodulin, a Marker of Endothelial Cell Injury, Using Quartz Crystal Microbalance.

Thrombomodulin (TM), an integral glycoprotein on the surface of endothelial cells, can be released during endothelial cell injury and the levels of serum TM are regarded as an important parameter of activity in vasculitides in vivo. Quantitative detection of TM and investigation on the release of soluble thrombomodulin (sTM) by the injured HUVEC-C cells using quartz crystal microbalance (QCM) were achieved in this work. Anti-antibody (AAb) and bovine serum albumin (BSA) were bound on gold nanoparticles (GNPs) to construct BSA-GNPs-AAb nanocomposites and they were characterized by transmission electron microscope, UV-vis, and infrared spectrophotometry, respectively. The capture of the nanocomposites on the TM antibody modified electrode, which was tested by scanning electron microscope, could result in a great decrease of the resonant frequency (f0). This binding was effectively inhibited by the beforehand immobilized TM proteins on the electrode surface due to the strong steric hindrance effect. It led to the decrease of the frequency changing extent. The relative frequency-shift was found to be proportional to the logarithm of the TM concentration from 10 to 5000 ng mL(-1) with a detection limit of 2 ng mL(-1). By analyzing the growth medium used for cell incubation, the release of sTM by the injured HUVEC-C cells in the presence of H2O2 was confirmed. The sTM amount in the growth medium was increased with the enhancement of contact time of the cells with H2O2, proving that sTM may serve as a specific marker of endothelial cell injury.

Computational Discovery of Intermolecular Singlet Fission Materials Using Many-Body Perturbation Theory.

Intermolecular singlet fission (SF) is the conversion of a photogenerated singlet exciton into two triplet excitons residing on different molecules. SF has the potential to enhance the conversion efficiency of solar cells by harvesting two charge carriers from one high-energy photon, whose surplus energy would otherwise be lost to heat. The development of commercial SF-augmented modules is hindered by the limited selection of molecular crystals that exhibit intermolecular SF in the solid state. Computational exploration may accelerate the discovery of new SF materials. The GW approximation and Bethe-Salpeter equation (GW+BSE) within the framework of many-body perturbation theory is the current state-of-the-art method for calculating the excited-state properties of molecular crystals with periodic boundary conditions. In this Review, we discuss the usage of GW+BSE to assess candidate SF materials as well as its combination with low-cost physical or machine learned models in materials discovery workflows. We demonstrate three successful strategies for the discovery of new SF materials: (i) functionalization of known materials to tune their properties, (ii) finding potential polymorphs with improved crystal packing, and (iii) exploring new classes of materials. In addition, three new candidate SF materials are proposed here, which have not been published previously.

Localized, highly efficient secretion of signaling proteins by migrasomes.

Migrasomes, enriched with signaling molecules such as chemokines, cytokines and angiogenic factors, play a pivotal role in the spatially defined delivery of these molecules, influencing critical physiological processes including organ morphogenesis and angiogenesis. The mechanism governing the accumulation of signaling molecules in migrasomes has been elusive. In this study, we show that secretory proteins, including signaling proteins, are transported into migrasomes by secretory carriers via both the constitutive and regulated secretion pathways. During cell migration, a substantial portion of these carriers is redirected to the rear of the cell and actively transported into migrasomes, driven by the actin-dependent motor protein Myosin-5a. Once at the migrasomes, these carriers fuse with the migrasome membrane through SNARE-mediated mechanisms. Inhibiting migrasome formation significantly reduces secretion, suggesting migrasomes as a principal secretion route in migrating cells. Our findings reveal a specialized, highly localized secretion paradigm in migrating cells, conceptually paralleling the targeted neurotransmitter release observed in neuronal systems.

Ant colony optimization-based adjusted PID parameters: a proposed method.

The ant colony algorithm (ACA) is a heuristic algorithm that resolves the optimality problem by simulating an ant's foraging process, which finds the shortest path. The connotation of the ACA is to find the optimal solution. The Proportional Integral Derivative (PID) parameter tuning is an essential tool in the control field and includes three parameters, Kp, Ki, and Kd, to achieve the best control effect. Besides, tuning the PID parameters is closely related to finding the "optimal" solution that can be attained based on the feasible combination of the two. This article transforms the PID parameter tuning problem into an ACA that finds the optimal solution called ACA-based PID parameters tuning. Furthermore, PID control is simulated by setting the parameters of ACA, such as ant colony size, iteration times, nodes, paths, path evaluation criteria, pheromone concentration, heuristic function, weight factor, and decision function. Eventually, the two PID controller parameter tuning strategies are compared and analyzed, and the advantages and disadvantages of each are obtained. Compared with the 4:1 attenuation curve method, the proposed method can significantly reduce the MP score of the overshoot of the system, increase the time, and improve the dynamic and steady-state performance of the system, but reduce the steady-state error of the system. Therefore, the feasibility and effectiveness of the proposed method is verified.

Activating transcription factor 3 inhibits angiotensin II­induced cardiomyocyte viability and fibrosis by activating the transcription of cysteine­rich angiogenic protein 61.

Depletion of activating transcription factor 3 (ATF3) expression has previously been reported to promote hypertrophy, dysfunction and fibrosis in stress overload­induced hearts; however, the mechanism involved remains poorly understood. In the present study, the mechanism underlying the activation of cysteine­rich angiogenic protein 61 (Cyr61) by ATF3 in hyperproliferative and fibrotic human cardiac fibroblasts (HCFs), induced by angiotensin II (Ang II), was evaluated. The mRNA and protein expression levels of ATF3 and Cyr61 were assessed using reverse transcription­quantitative PCR and western blotting, respectively. The Cell Counting Kit­8 assay was used to assess cell viability. Cell migration was assessed using the wound healing assay and western blotting, whereas the extent of cell fibrosis was evaluated using immunofluorescence staining and western blotting. The binding site of ATF3 to the Cyr61 promoter was predicted using the JASPAR database, and verified using luciferase reporter and chromatin immunoprecipitation assays. The results demonstrated that the mRNA and protein expression levels of ATF3 were significantly upregulated in Ang II­induced HCFs. Overexpression of ATF3 significantly inhibited the Ang II­induced viability, migration and fibrosis of HCFs, whereas ATF3 knockdown mediated significant opposing effects. Mechanistically, ATF3 was demonstrated to transcriptionally activate Cyr61. Cyr61 silencing was subsequently revealed to reverse the effects of ATF3 overexpression on HCFs potentially via regulation of the TGF­ß/Smad signaling pathway. The results of the present study suggested that ATF3 could suppress HCF viability and fibrosis via the TGF­ß/Smad signaling pathway by activating the transcription of Cyr61.

A Personalized Management Approach of OHSS: Development of a Multiphase Prediction Model and Smartphone-Based App.

Objective: This study aimed to develop multiphase big-data-based prediction models of ovarian hyperstimulation syndrome (OHSS) and a smartphone app for risk calculation and patients' self-monitoring. Methods: Multiphase prediction models were developed from a retrospective cohort database of 21,566 women from January 2017 to December 2020 with controlled ovarian stimulation (COS). There were 17,445 women included in the final data analysis. Women were randomly assigned to either training cohort (n = 12,211) or validation cohort (n = 5,234). Their baseline clinical characteristics, COS-related characteristics, and embryo information were evaluated. The prediction models were divided into four phases: 1) prior to COS, 2) on the day of ovulation trigger, 3) after oocyte retrieval, and 4) prior to embryo transfer. The multiphase prediction models were built with stepwise regression and confirmed with LASSO regression. Internal validations were performed using the validation cohort and were assessed by discrimination and calibration, as well as clinical decision curves. A smartphone-based app "OHSS monitor" was constructed as part of the built-in app of the IVF-aid platform. The app had three modules, risk prediction module, symptom monitoring module, and treatment monitoring module. Results: The multiphase prediction models were developed with acceptable distinguishing ability to identify OHSS at-risk patients. The C-statistics of the first, second, third, and fourth phases in the training cohort were 0.628 (95% CI 0.598-0.658), 0.715 (95% CI 0.688-0.742), 0.792 (95% CI 0.770-0.815), and 0.814 (95% CI 0.793-0.834), respectively. The calibration plot showed the agreement of predictive and observed risks of OHSS, especially at the third- and fourth-phase prediction models in both training and validation cohorts. The net clinical benefits of the multiphase prediction models were also confirmed with a clinical decision curve. A smartphone-based app was constructed as a risk calculator based on the multiphase prediction models, and also as a self-monitoring tool for patients at risk. Conclusions: We have built multiphase prediction models based on big data and constructed a user-friendly smartphone-based app for the personalized management of women at risk of moderate/severe OHSS. The multiphase prediction models and user-friendly app can be readily used in clinical practice for clinical decision-support and self-management of patients.

Generation of αGal-enhanced bifunctional tumor vaccine.

Hepatocellular carcinoma (HCC) is a common malignant tumor with poor prognosis and high mortality. In this study, we demonstrated a novel vaccine targeting HCC and tumor neovascular endothelial cells by fusing recombinant MHCC97H cells expressing porcine α-1,3-galactose epitopes (αGal) and endorphin extracellular domains (END) with dendritic cells (DCs) from healthy volunteers. END+/Gal+-MHCC97H/DC fusion cells induced cytotoxic T lymphocytes (CTLs) and secretion of interferon-gamma (IFN-γ). CTLs targeted cells expressing αGal and END and tumor angiogenesis. The fused cell vaccine can effectively inhibit tumor growth and prolong the survival time of human hepatoma mice, indicating the high clinical potential of this new cell based vaccine.

Clinical Application of Tumor Vascular Disrupting Therapy: A Systematic Review and Meta-Analysis.

PURPOSE: The occurrence, progression, invasion and metastasis of tumors depend on a tumor vascular network. Vascular disrupting agents (VDAs) are a new class of drugs targeting the tumor vasculature, by blocking the existing tumor blood vessels. However, there is no clear consensus on the clinical efficacy of tumor vascular disrupting therapy. In this study, we performed the first systematic review and meta-analysis of published clinical trials focused on tumor vascular disrupting therapies. MATERIALS AND METHODS: We searched PubMed, EMBASE, and the Cochrane Library to identify clinical trials that used VDAs to treat tumors. After literature screening and data extraction, according to inclusion and exclusion labels, meta-analysis was performed using RevMan5.3 software. RESULTS: In this meta-analysis, we included 2659 patients from eight randomized controlled trials involving non-small-cell lung cancer, prostate, epithelial ovarian, fallopian tube, and primary peritoneal carcinoma. Compared with the control arm, the experimental arm exhibited an effective improvement of 0.5-year and 1-year survival, as well as the 6-month progression-free survival rate. There was no significant difference between patients in the experimental compared to the control arm with respect to objective response and disease control rates, and 12-month progression-free survival. CONCLUSION: Vascular disrupting therapy can effectively prolong the survival of cancer patients. However, for indicators of short-term efficacy, such as objective response rate and disease control rate, there is still a lack of high-quality, large-scale clinical trial data to confirm the effectiveness of VDAs.

BSA-Coated Gold Nanorods for NIR-II Photothermal Therapy.

The second near infrared window is considered to be the optimal optical window for medical imaging and therapy as its capability of deep tissue penetration. The preparation of the gold nanorods with long wavelength absorption and low cytotoxicity is still a challenge. A series gold nanorods with large aspect ratio have been synthesized. Strong plasma absorption in the second near infrared window from 1000 to 1300 nm could be observed. The biocompatibility of the synthesized gold nanorods is dramatically improved via coating by bovine serum albumin (BSA), while the optical properties of which remains. The breast cancer tumor-bearing mouse could be well treated by the prepared gold nanorods with the NIR-II light intensity as low as 0.75 W/cm2. In summary, these results demonstrate the feasibility of using low illumination dose to treat tumor in the NIR-II region via the large aspect ratio gould nanoparticles.

Spatial occurrence and composition profile of organophosphate esters (OPEs) in farmland soils from different regions of China: Implications for human exposure.

The environmental load of organophosphate ester (OPE) flame retardants has caused a series of problems due to their extensive use. The soil matrix, as an ultimate sink for organic pollution, plays a vital part in the fate of OPEs in the environment. In this study, the spatial occurrence, composition profile and health risk of 13 OPE species in farmland soils from four provinces of China were characterized. Excluding tris(2,3-dibromopropyl) phosphate (TDBPP) and ethylhexyl diphenyl phosphate (EHDPP), the remaining eleven OPEs had a high detection frequency (DF) ranging from 60% to 100%. The range of total OPE (ΣOPE) concentrations were 62.3-394 ng/g dry weight (dw), with a median of 228 ng/g dw. Among these OPEs, tris(2-ethylhexyl) phosphate (TEHP) with a median of 143 ng/g dw) was the predominant species, followed by tricresyl phosphate (TCP; median of 20.1 ng/g dw) and tris(2-chloroethyl) phosphate (TCEP; median of 17.9 ng/g dw). In terms of geographical distribution, significantly lower OPEs levels were found in samples from Heilongjiang (159 ± 47.0 ng/g dw) than in those of Guangxi (264 ± 66.0 ng/g dw), Henan (252 ± 74.5 ng/g dw) and Hubei (242 ± 52.8 ng/g dw) provinces. Principal component analysis and Spearman's correlations were used to reveal potential sources of OPEs in the different provincial regions. Health risk exposure to OPEs in farmland soils was at an acceptable level (<1.20 × 10-5 for non-carcinogenic risk to children as the most sensitive age group; and <6.47 × 10-10 for carcinogenic risk to adults as the most sensitive age group) at the present detected concentrations. However, TCEP and TEHP, the predominant risk contributors, should be paid more attention.

Application of Molecular Nanoprobes in the Analysis of Differentially Expressed Genes and Prognostic Models of Primary Hepatocellular Carcinoma.

Analyzing hub genes related to tumorigenesis based on biological big data has recently become a hotspot in biomedicine. Nanoprobes, nanobodies and theranostic molecules targeting hub genes delivered by nanocarriers have been widely applied in tumor theranostics. Hepatocellular carcinoma (HCC) is one of the most common cancers, with a poor prognosis and high mortality. Identifying hub genes according to the gene expression levels and constructing prognostic signatures related to the onset and outcome of HCC will be of great significance. In this study, the expression profiles of HCC and normal tissue were obtained from the GEO database and analyzed by GEO2R to identify DEGs. GO terms and KEGG pathways were enriched in DAVID software. The STRING database was consulted to find protein-protein interactions between proteins encoded by the DEGs, which were visualized by Cytoscape. Then, overall survival associated with the hub genes was calculated by the Kaplan-Meier plotter online tool, and verification of the results was carried out on TCGA samples and their corresponding clinical information. A total of 603 DEGs were obtained, of which 479 were upregulated and 124 were downregulated. PPI networks including 603 DEGs and 18 clusters were constructed, of which 7 clusters with MCODE score ≥3 and nodes ≥5 were selected. The 5 genes with the highest degrees of connectivity were identified as hub genes, and a prognostic model was constructed. The expression and prognostic potential of this model was validated on TCGA clinical data. In conclusion, a five-gene signature (TOP2A, PCNA, AURKA, CDC20, CCNB2) overexpressed inHCC was identified, and a prognostic model was constructed. This gene signature may act as a prognostic model for HCC and provide potential targets of nanotechnology.

Generation of in situ CRISPR-mediated primary and metastatic cancer from monkey liver.

Non-human primates (NHPs) represent the most valuable animals for drug discovery. However, the current main challenge remains that the NHP has not yet been used to develop an efficient translational medicine platform simulating human diseases, such as cancer. This study generated an in situ gene-editing approach to induce efficient loss-of-function mutations of Pten and p53 genes for rapid modeling primary and metastatic liver tumors using the CRISPR/Cas9 in the adult cynomolgus monkey. Under ultrasound guidance, the CRISPR/Cas9 was injected into the cynomolgus monkey liver through the intrahepatic portal vein. The results showed that the ultrasound-guided CRISPR/Cas9 resulted in indels of the Pten and p53 genes in seven out of eight monkeys. The best mutation efficiencies for Pten and p53 were up to 74.71% and 74.68%, respectively. Furthermore, the morbidity of primary and extensively metastatic (lung, spleen, lymph nodes) hepatoma in CRISPR-treated monkeys was 87.5%. The ultrasound-guided CRISPR system could have great potential to successfully pursue the desired target genes, thereby reducing possible side effects associated with hitting non-specific off-target genes, and significantly increasing more efficiency as well as higher specificity of in situ gene editing in vivo, which holds promise as a powerful, yet feasible tool, to edit disease genes to build corresponding human disease models in adult NHPs and to greatly accelerate the discovery of new drugs and save economic costs.

PEGylated immunoliposome-loaded endoglin single-chain antibody enhances anti-tumor capacity of porcine α1,3GT gene.

Tumor could not be completely removed due to the absence of immune storm against tumor. The porcine α1,3 galactosyltransferase (α1,3 GT) induce the hyperacute rejection by synthesizing Galα1-3Galß1-(3)4GlcNAc-R (αGal) on the surface of graft endothelial cells (ECs) during xeno-transplantation. This study aimed to develop anti-endoglin single-chain Fv fragments (ENG-scFv) conjugated PEGylated immunoliposomes (iLPs) to induce immune storm against tumor. Immune fluorescence was performed to detect the binding of ENG-scFv to human ENG, the endosomal/lysosomal escape of ENG-scFv-iLPs/α1,3 GT, and αGal expression in hENG-HEK293 cells. In vitro MTT assay was performed to measure ENG-scFv-iLPs/α1,3 GT cytotoxicity. NOD/SCID mouse born A549 tumor model was used to evaluate the therapeutic potency of ENG-scFv-iLPs/α1,3 GT. ENG-scFv-iLPs enabled efficient targeting delivery of α1,3 GT plasmid to ENG + tumors neovascular endothelial cells (TnECs), promoted endosomal/lysosomal escape due to the pH-sensitive ability, then synthesized carbohydrate epitope αGal on the surface of these cells to achieve the purpose of destroying the tumor. The mechanism of uptake for nanoparticles was energy driven, the clathrin-mediated endocytosis was the main endocytic pathway of the ENG-mAb-iLPs/α1,3 GT and lipid-raft-mediated of the ENG-scFv-iLPs/α1,3 GT, and macropinocytosis was also involved in intracellular entry. The inhibition of tumor angiogenesis and proliferation by ENG-scFv-iLPs/α1,3 GT was closely related to down-regulation of VEGF. Our findings establish an alternative therapeutic paradigm for scFv-conjugated nanoparticles to induce tumor cell apoptosis and inhibit tumor growth early. Such iLPs nanocarrier could efficiently release α1,3 GT to their distinct sites of action, where the endoglin + tumor neovascular endothelial cells (ENG + TnECs) exist, in a site-specific manner. Therefore, we believe that these scFv-targeted core-shell immunocomplexes are an important potential α1,3 GT delivery system for various solid tumor-targeted therapy.

A Dual Targeting Magnetic Nanoparticle for Human Cancer Detection.

Malignant tumors are a major threat to human life and high lymphatic vessel density is often associated with metastatic tumors. With the discovery of molecules targeted at the lymphatic system such as lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) and Podoplanin, many studies have been performed to determine the role of lymphatic endothelial cells (LECs) in tumor metastasis. However, disadvantages such as non-specificity and high cost limit their research and diagnostic applications. In this study, Fe3O4@KCTS, a core-shell type of magnetic nanoparticles, was prepared by activating Fe3O4 with carbodiimide and cross-linking it with α-ketoglutarate chitosan (KCTS). The LYVE-1 and Podoplanin antibodies were then incorporated onto the surface of these magnetic nanoparticles and as a result, dual-targeting magnetic nanoprobes were developed. The experimental tests of this study demonstrated that a dual-targeting magnetic nanoprobe with high-purity LECs from tumor tissues was successfully developed, providing a basis for clinical application of LECs in colorectal cancer treatment as well as in early clinical diagnosis using bimodal imaging.

Non-enzymatic detection of glucose using poly(azure A)-nickel modified glassy carbon electrode.

A simple, sensitive and selective non-enzymatic glucose sensor was constructed in this paper. The poly(azure A)-nickel modified glassy carbon electrode was successfully fabricated by the electropolymerization of azure A and the adsorption of Ni(2+). The Ni modified electrode, which was characterized by scanning electron microscope, cyclic voltammetry, electrochemical impedance spectra and X-ray photoelectron spectroscopy measurements, respectively, displayed well-defined current responses of the Ni(III)/Ni(II) couple and showed a good activity for electrocatalytic oxidation of glucose in alkaline medium. Under the optimized conditions, the developed sensor exhibited a broad linear calibration range of 5 µM-12mM for quantification of glucose and a low detection limit of 0.64µM (3σ). The excellent analytical performance including simple structure, fast response time, good anti-interference ability, satisfying stability and reliable reproducibility were also found from the proposed amperometric sensor. The results were satisfactory for the determination of glucose in human serum samples as comparison to those from a local hospital.

Label-free electrochemical immunoassay of Bcl-2 protein expression on tumor cells.

Bcl-2 protein is one of the anti-apoptotic members in Bcl-2 family proteins. It can regulate apoptosis in response to a wide variety of toxic agents, which has a close relationship with drug-resistance of tumor cells. Electrochemical impedance spectroscopy measurements were employed to quantify the cell concentration and analyze the expression of Bcl-2 protein on tumor cells and drug-resistant tumor cells based on the competitive immunoassay. Bcl-2 antibody and bovine serum albumin were adsorbed on Au nanoparticles to construct nanocomposites that could be captured on the Bcl-2 protein modified electrode. The binding of the nanocomposites resulted in a great increase of the charge-transfer resistance (Rct) due to the strong steric hindrance effect and this effect was inhibited in the presence of MCF-7 cells and MCF-7/ADR cells owing to the competitive immunoreaction between the nanocomposites and Bcl-2 proteins on cells. Under the optimal conditions, the charge-transfer resistance change (ΔRct) is proportional to the logarithm of the cells concentration from 5×10(2) to 1.6×10(6) cell mL(-1) with a detection limit of 170 cell mL(-1). The expression of Bcl-2 protein on MCF-7/ADR cells was found to be significantly higher than that in MCF-7 cells, indicating that the up-regulation of Bcl-2 protein is one of characteristics of drug-resistant tumor cells.