Scientific Reports
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2020
·Vol. 10
·期 1
·1-14
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IF 3.998
Zhang Chao,Zhang Fanghua,Han Mengnan,Wang Xuming,Du Jie,Zhang Honglei,Li Wei
Combination chemotherapy is still of great importance as part of the standard clinical care for patients with HER2 positive breast cancer. As an attractive component, gold nanoparticles (AuNPs) have been extensively studied as biosafety nanomaterials, but they are rarely explored as drug nanocarriers for targeted co-delivery of multiple chemotherapeutics. Herein, a novel affibody-DNA hybrid strands modified AuNPs were fabricated for co-loading nucleoside analogue (5-fluorodeoxyuridine, FUdR) and anthracycline (doxorubicin, Dox). FUdRs were integrated into DNA hybrid strands decorated on AuNPs by DNA solid phase synthesis, and Dox molecules were intercalated into their duplex regions. Affibody molecules coupled to the DNA hybrid strands were distributed the surface of AuNPs, giving them targeting for HER2. The new dual-drug-containing affibody-DNA-AuNPs (Dox@affi-F/AuNPs) owned compact and stable spherical nanostructures, and precise drug loading. Cytotoxicity tests demonstrated that these nanoparticles caused a higher inhibition in HER2 overexpressing breast cancer cells, and showed better synergistic antitumor activity than simple mixture of the two drugs. The related mechanistic studies proved that Dox@affi-F/AuNPs achieved a remarkable combined antitumor activity of Dox and FUdR by promoting more cells to enter apoptosis pathway. Our work provided a nanomedicine platform for targeted co-delivery of nucleoside analog therapeutics and anthracycline anticancer drugs to achieve synergistic treatment of HER2 + cancer.
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COLLOIDS AND SURFACES B-BIOINTERFACES
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2024
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IF 5.4
Ying Li,Meiqi Qian,Yuping Cheng,Xue Qiu
In situ cell imaging plays a crucial role in studying physiological and pathological processes of cells. Proximity ligation assay (PLA) and rolling circle amplification (RCA) are commonly used to study the abundance and interactions of biological macromolecules. The most frequently applied strategy to visualize the RCA products is with single-fluorophore probe, however, cellular auto-fluorescence and unbound fluorescent probes could interfere with RCA products, leading to non-specific signals. Here, we present a novel approach combining aptamer mediated PLA, RCA, and Förster Resonance Energy Transfer (FRET), namely Apt-PLA-RCA-FRET, for sensitive in situ imaging and analysis of the abundances and interactions of membrane proteins such as tetraspanin CD63 and human epidermal growth factor receptor 2 (HER2). Apt-RCA-FRET was initially designed to show its ability to assess the abundance of target proteins on different cells. Dual functional oligonucleotides served as both the aptamer for recognizing specific membrane proteins and the primer of circular DNA for following RCA process, and the resulting RCA products were subsequently imaged by FRET signals from Cy3 to Cy5 probes which hybridized sequentially on them. FRET was demonstrated to show its great potential to resist the interferences of nonspecific fluorescence compared to single-fluorophore strategies. PLA was then introduced to Apt-RCA-FRET to investigate the spatial localization of different proteins on cell membrane and their interactions. Our approach utilizing aptamer as membrane proteins recognition element simply converted the abundance of proteins into nucleic acid signals and facilitated the following signal amplification, thus it serves as an important alternative to methods typically based on antibody and presents a more robust and sensitive method for analyzing the abundances of different cell membrane proteins and their spatial localization, which offers valuable insights into physiological and pathological processes of cells.
研究领域:
细胞生物学
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分子生物学
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生物医学工程
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分析化学
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Chemistry Africa-A Journal of the Tunisian Chemical Society
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2026
·Vol. 9
·期 1
·36
·
IF 2.2
Mohsin Dheyaa Hussein,Ali Jassim Mohammed,Ahmed Tamara N.,AL-Mayah Saif Jabbar Yasir
The urgent need for precise quantification of a crucial prognostic tumor marker, a human epidermal growth factor receptor 2 (HER2), is of paramount importance for health institutions in screening, diagnosis, and the therapeutic trip of breast cancer. A conspicuous analysis of the extracellular domain of the human epidermal growth factor receptor 2 (HER2-ECD) was conducted using a sandwich electrochemical immunosensing assay on nanomaterial-modified screen-printed carbon electrode (SPCE) surfaces. The SPCEs modified with carboxylated multiwalled carbon nanotubes combined with Fe/Cu bimetallic 1,4-benzenedicarboxylic acid metal-organic frameworks loaded with AgNPs as a sensing platform for carrying capture antibody. The antibody-antigen interaction was identified utilizing horseradish peroxidase (HRP) conjugated detection antibody and 3,3’,5,5’-tetramethylbenzidine (TMB) as the enzymatic substrate. The structural, compositional, and morphological properties of synthesized nanomaterials were characterized by ( FT.IR, XRD, EDX, and FESEM ), before evaluating the analytical performance. The electrochemical signals were obtained by cyclic voltammetry, differential pulse voltammetry, and square wave voltammetry. Linear calibration plots were generated between 20 and 200 pg/mL, and limits of detection (LODs) were identified to be of 5.5 pg/mL, 5.65 pg/mL, and 3.96 pg/mL (for CV, DPV, and SWV), respectively, all much below the defined cut-off value of 15 ng/mL for this cancer biomarker. An immunosensor that had been designed expressly for the purpose of detecting the tumor marker in serum was utilized in order to conduct an experimental evaluation of the procedure’s effectiveness.
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International Journal of Pharmaceutics-X
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2024
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IF 5.2
Xing Liu,Wenwen Shen
In this study, the trastuzumab-functionalized SK-BR-3 cell membrane-wrapped mesoporous silica nanoparticles loaded with pyrotinib (Tra-CM-MSN-PYR) were prepared for targeted therapy of HER2-positive breast cancer. Transmission electron microscopy (TEM) characterization showed that MSN had a spherical morphology with mesoporous channels and that the structure of Tra-CM-MSN was a cell membrane (CM) layer successfully coated on the surface of MSN. A cellular uptake assay demonstrated that FITC-labeled Tra-CM-MSN were taken up by SK-BR-3 breast cancer cells, which illustrated that Tra-CM-MSN had good targeting ability compared with CM-MSN and MSN. In vivo imaging experiments demonstrated significant accumulation of FITC-labeled Tra-CM-MSN in tumor tissues, further proving that Tra-CM-MSN have superior targeting properties. Cell apoptosis experiments suggested that Tra-CM-MSN-PYR significantly inhibited the proliferation of SK-BR-3 breast cancer cells. The results of in vivo animal experiments also showed that Tra-CM-MSN-PYR significantly inhibited tumor growth. These results indicate that Tra-CM-MSN-PYR has potential application as a targeted therapy for HER2-positive breast cancer in the future.
研究领域:
药学
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纳米技术
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肿瘤学
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生物医学工程
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BIOSENSORS & BIOELECTRONICS
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2019
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IF 9.518
Xiaoxi Guo,Shuping Liu,Minghui Yang,Huitong Du,Fengli Qu
Photoelectrochemical (PEC) biosensor for highly sensitive detection of breast cancer biomarker human epidermal growth factor receptor-2 (HER2) is reported utilizing a dual signal amplification strategy. The biosensor was prepared based on tungsten sulfide nanowire array on Ti mesh (WS 2 NW/TM). Such WS 2 NW/TM electrode can generate photoelectric signal under visible light excitation . The HER2 aptamer was wrapped onto the nanowire array surface for specific binding with HER2 molecules, and gold nanoparticles (Au NPs) that modified with glucose oxidase (GOx) and HER2 binding peptide was utilized for signal amplification. The H 2 O 2 that generated by GOx catalyzed glucose reaction and localized surface plasmon resonance of Au NPs can both enhance the PEC current intensity of the biosensor, leading to dual signal amplification. The PEC current intensity is enhanced linearly with HER2 concentration in the 0.5–10 ng/mL range with limit of detection of 0.36 ng/mL. Such biosensor was applied for the detection of HER2 in breast cancer serum samples with detection results in good agreement with commercial ELISA results.
研究领域:
生物医学工程
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纳米技术
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癌症生物学
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分析化学
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