查找使用阿拉丁产品的科研文献

A dual-aptamer-based biosensor for specific detection of breast cancer biomarker HER2 via flower-like nanozymes and DNA nanostructures

Dan Ou,Duanping Sun,Xiangan Lin,Zhixian Liang,Yongsheng Zhong,Zuanguang Chen

Developing highly sensitive and selective detection strategies for biomarkers is beneficial for fundamental research and disease diagnosis. Herein, we constructed a sandwich-type electrochemical aptasensor to detect the breast cancer cell biomarker Human Epidermal Growth Factor Receptor 2 (HER2). The aptasensor was a combination of tetrahedral DNA nanostructures (TDNs)–aptamer as recognition probes and flower-like nanozymes/horseradish peroxidase (HRP) as signal nanoprobes. In the process of assembling the biosensor, the TDN–aptamer 1 as a bio-recognition element was immobilized on the gold electrode (GE) surface for capturing the biomarker HER2. The nanozyme Mn3O4 was decorated by Pd@Pt nanozymes which were linked by the aptamer 2 and natural enzyme HRP. The designed Mn3O4/Pd@Pt/HRP nanoprobe (nanoprobe 1) was used to amplify the biosensor signal via catalyzing the oxidation of hydroquinone (HQ) with hydrogen peroxide (H2O2). After binding HER2, an aptamer–protein–nanoprobe sandwich system was fabricated on the GE surface. Lastly, a Pd@Pt/HRP/complementary DNA (cDNA) nanoprobe (nanoprobe 2) was added on the surface of nanoprobe 1 through DNA hybridization of aptamer 2 and cDNA to form a dendritic DNA nanostructure to further amplify the signal significantly. The results indicate that the aptasensor shows a broad linear response from 0.1 to 100.0 ng mL−1 and the low detection limit is 0.08 ng mL−1. The designed approach holds great potential for the construction of various aptasensors for the effective and convenient detection of different biomarkers.

Fabrication of Bioconjugates Clacked Chitosan-Coated SN-38 Liposomal Nanoparticles: Improved Precise Chemotherapy Efficacy in Lung Cancer Cells and Its Apoptosis

Xiaojun Zhang,Wei Sun,Changting Liu

Employing an active targeting method with monoclonal antibodies for chemotherapeutics-loaded nanocarriers represents a promising option to enhance the specific drug delivery and alleviate the detrimental effects of chemotherapeutic agents. Targeted delivery to the human epidermal growth factor receptor-2 (HER2), which is overexpressed in HER2+ lung cancerous cells, can be accomplished by conjugating nanoparticles with a monoclonal antibody (anti-HER2). We developed trastuzumab (TZ)-conjugated chitosan iodoacetamide (CsIA)-coated liposomal nanoparticles carrying SN-38 (TZ-SN-CsIA LNPs) as a lung-targeted delivery. CsIA was used to develop trastuzumab-clacked nanoparticles (TZ LNPs). The structure, physicochemical characteristics, SN-38 encapsulation, SN-38 release, and anticancer properties of the LNPs were established. The TZ LNPs were spherical, measuring around 77 nm in diameter, and exhibited a positive zeta potential; upon drug incorporation, the diameter of the TZ LNPs enlarged. A sustained, 24-h SN-38 release from the nanocarriers was accomplished. TZ LNPs demonstrated substantial cellular accumulation and markedly enhanced anticancer efficacy against HER2+ Calu-3 lung adenocarcinoma cancer cells compared to the drug solution and unconjugated LNPs. Consequently, TZ-SN-CsIA LNPs may be a potential nanocarrier for HER2+ lung cancer.

Electrochemiluminescence Aptasensor for HER2-ECD Detection Based on Resonance Energy Transfer between AuPt@ZIF-67 and AuNPs/g-C3N4/PDDA Composites

Hui Zhong,Yonghua Yuan,Min Qing,Jianli Zuo,Yueyuan Li,Lijuan Bai

The extracellular domain of the human epidermal growth factor receptor (HER2-ECD) is a breast cancer biomarker. Accurate and sensitive detection of HER2-ECD concentration in serum is crucial in the diagnosis and patient follow-up. Herein, an “off–on” type electrochemiluminescence (ECL) aptasensor based on the resonance energy transfer (RET) between AuPt@ZIF-67 and AuNPs/g-C3N4/PDDA was developed for detecting HER2-ECD. First, AuNP-modified g-C3N4 (AuNPs/g-C3N4/PDDA), as a signal substrate, generates ECL signals under the co-reactant peroxodisulfate (S2O82–) in a specific potential range and shows significantly enhanced signal strength and stability. Then, AuPt@ZIF-67 expeditiously quenched the ECL signal of AuNPs/g-C3N4/PDDA because of ECL resonance energy transfer (ECL-RET) between AuPt@ZIF-67 and AuNPs/g-C3N4/PDDA. We designed a new aptasensor detection platform for HER2-ECD detection. After specific binding of the aptamer with HER2-ECD, the AuPt@ZIF-67 content in the system decreased, and the ECL response recovered. The biosensor demonstrated a linear range of HER2-ECD detection between 100 fg/mL and 100 ng/mL under ideal circumstances, with a low detection limit of 17.3 fg/mL. Furthermore, this biosensor was successfully tested in human serum samples. This strategy, as a novel ECL system with satisfactory stability and excellent sensitivity, can realize the detection of other biological molecules by changing the probe, which is a promising method.

An electrochemical biosensor for HER2 detection in complex biological media based on two antifouling materials of designed recognizing peptide and PEG

Xiqin Yang,Ping Chen,Xi Zhang,Hao Zhou,Zhen Song,Wenlong Yang,Xiliang Luo

A simple tactic for electrochemical determination of a typical biomarker for breast cancer, human epidermal growth factor receptor 2 (HER2), was presented via the construction of a low fouling sensing interface functionalized with polyethylene glycol (PEG) and peptide. The HER2 biosensor was developed based on an electrode modified by the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) and Au nanoparticles (AuNPs) as the sensing substrate, and followed by the immobilization of an antifouling PEG and a peptide with both recognizing and antifouling properties. Thanks to the combined antifouling effect of the PEG and peptide, and the specific recognizing ability of the peptide to the target HER2, the developed electrochemical biosensor exhibited strong antifouling performances in complex biofluids, such as human blood and serum, and it was capable of assaying target HER2 within a very wide linear range (1.0 pg mL −1 to 1.0 μg mL −1 ), with an ultralow limit of detection (0.44 pg mL −1 ). The combination of two kinds of antifouling biomaterials (PEG and peptide) offered an effective strategy for the development of low fouling sensing platforms suitable for practical assay in complex biotic environments.

Herceptin-functionalized SK-BR-3 cell membrane-wrapped paclitaxel nanocrystals for enhancing the targeted therapy effect of HER2-positive breast cancer

Qian Wu,Le Tong,Zhiru Zou,Yingqiao Li,Jinyu An,Wenwen Shen,Yu Gao,Ying Liu,Chao Wu

The objective of this study was to prepare Herceptin-functionalized SK-BR-3 cell membrane-wrapped paclitaxel nanocrystals (HCNCs) as a targeted delivery module for HER2-positive breast cancer. According to transmission electron microscopy (TEM) images, HCNCs presented a membrane-coated cubic shape with a particle size of approximately 220 nm. In vitro release test suggested that HCNCs had a certain sustained release effect of paclitaxel (PTX). Cell uptake experiments, in vivo imaging, and tissue distribution experiments demonstrated that HCNCs had excellent targeting ability to homologous tumor cells (SK-BR-3). The results of MTT, flow cytometry, Western blot, cell immunofluorescence staining, and in vivo antitumor experiments proved that HCNCs had a more significant ability to promote HER2-positive breast cancer cell apoptosis and inhibit its proliferation. These results clearly concluded that HCNCs were a promising nano-targeted preparation in anti-HER2-positive breast cancer.

Targeted Fe-doped silica nanoparticles as a novel ultrasound–magnetic resonance dual-mode imaging contrast agent for HER2-positive breast cancer

Xiaoyu Li,Shujun Xia,Wei Zhou,Ri Ji,Weiwei Zhan

Synthesis and Feasibility Evaluation of a new Trastuzumab Conjugate Integrated with Paclitaxel and 89Zr for Theranostic Application Against HER2-Expressing Breast Cancers

Joo Hee Jang,Sang Jin Han,Jung Young Kim,Kwang Il Kim,Kyo Chul Lee,Chi Soo Kang

Graphical Conjugate for double duty : A new antibody-drug conjugate composed of paclitaxel (PTX), deferoxamine (DFO) and trastuzumab (DFO-trastuzumab-PTX) was prepared using simple conjugation chemistry. The new conjugate displayed instant complexation kinetics with 89 Zr and showed feasible cytotoxic effect and binding property on HER2-positive MDA-MB-231 breast cancer cell showing promising potential as a theranostic agent utilizing chemo-drug and positron emission tomography (PET). The preparation and in vitro evaluation of a theranostic conjugate composed of trastuzumab, paclitaxel (PTX), and deferoxamine (DFO)-chelated 89 Zr have been reported. These comounds have potential applications against HER2 receptor positive breast cancers. We conjugated DFO and PTX to trastuzumab by exploiting simple conjugation chemistry. The conjugate (DFO-trastuzumab-PTX) showed excellent radiolabeling efficiency with 89 Zr and the labeled conjugate had high in vitro stability in human serum. Furthermore, DFO-trastuzumab-PTX displayed comparable cytotoxicity with PTX and 89 Zr-DFO-trastuzumab-PTX exhibited HER2 receptor-mediated binding on HER2-positive MDA-MB-231 breast cancer cells. The results of our in vitro study indicate high potential of 89 Zr-DFO-trastuzumab-PTX to be utilized in the theranostic application against HER2-postive breast cancers.

Construction of pH/reduction dual responsive MSN-HAgel containing HApt for tumor targeting carriers

Yehong Liu,Miaoxin Chen,Gaoyang Li,Shouhong Xu,Honglai Liu

In this study, a pH/reduction dual responsive carrier containing 42nt-nucleic acid HApt based on mesoporous silica nanoparticles (MSNs) was designed. Two kinds of low molecular weight oligomeric hyaluronic acid (HA) were used to graft onto MSN for better drug encapsulation. Crosslinked MSN-HA3000gel and MSN-HA11000gel were prepared by crosslinking the HA chain through the sulfhydrylization of the carboxyl group on the HA side chain. An appropriate amount of sulfhydryl nucleic acid (HApt-SH) was added during the crosslinking reaction, which realized the targeting ability and apoptosis function to cancer cells overexpressing the HER2 receptor. Crosslinked HA had a good effect on decreasing the side effect of DOX that the drug leakage was less than 20% under a normal body environment. However, it could realize rapid and efficient drug release in a tumor environment. As to the release of HApt, it exhibited a good response to GSH. The cytotoxicity test showed that HApt contained in HAgel had a great targeting effect and significant cytotoxicity to SKBR3 cells. As a whole, this MSN-HAgel enabled the combination of gene therapy and chemotherapy, showing the synergistic effect of “1 + 1 > 2”, providing a novel idea for cancer treatments.

A sandwich-type electrochemical immunosensor for sensitive detection of HER2 based on dual signal amplification of La-MOF-PbO2 and PEI-MoS2NFs composites

Qin Xia,Zhaode Mu,Min Qing,Jing Zhou,Lijuan Bai

In recent decades, the incidence of breast cancer has increased year by year, posing a serious threat to human health and quality of life, and about 30% of breast cancer patients have human epidermal growth factor receptor 2 (HER2) overexpression. Therefore, HER2 has become an important biomarker and indicator for the clinical evaluation of breast cancer in diagnosis, prognosis and recurrence. In this work, polyethyleneimine functionalized MoS 2 nanoflowers (PEI-MoS 2 NFs) with good electrical conductivity and abundant active binding sites were designed and employed as a sensing platform for immobilizing the primary antibody of HER2 (Ab 1 ). In addition, a La-MOF-PbO 2 composite with a large specific surface area and good conductivity was used to load lots of electroactive toluidine blue (TB) and the secondary antibody of HER2 (Ab 2 ) via gold nanoparticles (AuNPs) as the linker. Thus, the constructed sandwich-type electrochemical immunosensor was applied for sensitive detection of HER2, which showed a wide linear range from 100 fg mL −1 to 10 μg mL −1 with a lower limit of detection of 15.64 fg mL −1 . Therefore, the resulting immunosensor in this study would have a potential application in clinical bioanalysis.

Enzyme catalysis enhanced dark-field imaging as a novel immunohistochemical method

Lin Fan,Yanyan Tian,Rong Yin,Doudou Lou,Xizhi Zhang,Meng Wang,Ming Ma,Shouhua Luo,Suyi Li,Ning Gu,Yu Zhang

Conventional immunohistochemistry is limited to subjective judgment based on human experience and thus it is clinically required to develop a quantitative immunohistochemical detection. 3,3′-Diaminobenzidin (DAB) aggregates, a type of staining product formed by conventional immunohistochemistry, were found to have a special optical property of dark-field imaging for the first time, and the mechanism was explored. On this basis, a novel immunohistochemical method based on dark-field imaging for detecting HER2 overexpressed in breast cancer was established, and the quantitative analysis standard and relevant software for measuring the scattering intensity was developed. In order to achieve a more sensitive detection, the HRP (horseradish peroxidase)-labeled secondary antibodies conjugated gold nanoparticles were constructed as nanoprobes to load more HRP enzymes, resulting in an enhanced DAB deposition as a dark-field label. Simultaneously, gold nanoparticles also act as a synergistically enhanced agent due to their mimicry of enzyme catalysis and dark-field scattering properties.

Affibody Modified G-quadruplex DNA Micelles Incorporating Polymeric 5-Fluorodeoxyuridine for Targeted Delivery of Curcumin to Enhance Synergetic Therapy of HER2 Positive Gastric Cancer

Chao Zhang,Shuangqing Fu,Fanghua Zhang,Mengnan Han,Xuming Wang,Jie Du,Honglei Zhang,Wei Li

Combination chemotherapy is emerging as an important strategy for cancer treatment with decreased side effects. However, chemotherapeutic drugs with different solubility are not easy to realize co-delivery in traditional nanocarriers. Herein, an affibody modified G-quadruplex DNA micellar prodrug (affi-F/GQs) of hydrophilic 5-fluorodeoxyuridine (FUdR) by integrating polymeric FUdRs into DNA strands is developed for the first time. To achieve synergistic efficacy with hydrophobic drugs, curcumin (Cur) is co-loaded into affi-F/GQs micelles to prepare the dual drug-loaded DNA micelles ([email protected]/GQs), in which affibody is employed as a targeting moiety to facilitate HER2 receptor-mediated uptake.[email protected]/GQs have a small size of approximately 130 nm and exhibit excellent stability. The system co-delivers FUdR and Cur in a ratiometric manner, and the drug loading rates are 21.1% and 5.6%, respectively. Compared with the physical combination of FUdR and Cur,[email protected]/GQs show higher cytotoxicity and greater synergistic effect on HER2 positive gastric cancer N87 cells. Surprisingly,[email protected]/GQs significantly enhance the expression and activity of apoptosis-associated proteins in Bcl-2/Bax-caspase 8, 9-caspase 3 apoptotic pathway, which is the main factor in the death of tumor cells induced by FUdR. Overall, this nanoencapsulation is a promising candidate for the targeted co-delivery of drugs with significant differences in solubility.Keywords:G-quadruplex;DNA micelles;affibody;5-fluorodeoxyuridine;curcumin;synergetic therapy

Optical biosensor based on weak value amplification for the high sensitivity detection of Pertuzumab in combination with Trastuzumab binding to the extracellular domain of HER2

Dongmei Li,Chaofan Weng,Chaoyi Chen,Kan Li,Qiang Lin,Yi Ruan,Yi Ruan,Jingjing Zhang,Shuqian Wang,Jia Yao,Jia Yao

A real-time optical phase sensing scheme based on weak value amplification was proposed to monitor the especially binding process of Pertuzumab combined with Trastuzumab on HER2 positive cells. From the wavelength shift of output spectrum, the phase difference between measuring and referential path related to the concentration of Pertuzumab as well as Trastuzumab could be calculated. With this approach, the limit of detection (LOD) of 5.54 × 10−13 M for Pertuzumab assay was achieved. Besides, the kinetics signal of Pertuzumab in combination with Trastuzumab binding to HER2 was detected in real time. Experimental results demonstrated that both Trastuzumab and Pertuzumab can be captured by HER2, but the former was significantly superior to the latter in terms of the target number. Additionally, the binding speed was analyzed and demonstrated to be closely correlated with the initial concentration of the targeting agents.