Frontiers in Oncology
·
2021
·
IF 6.244
Wen Li,Xia Lei,Guo Xiaoyi,Huang Hai-Feng,Wang Feng,Yang Xian-teng,Yang Zhi,Zhu Hua
Trastuzumab is a monoclonal antibody targeting human epidermal growth factor 2 (HER2), which has been successfully used in the treatment of patients with breast cancer and gastric cancer; however, problems concerning its cardiotoxicity, drug resistance, and unpredictable efficacy still remain. Herein, we constructed novel organic dopamine–melanin nanoparticles (dMNs) as a carrier and then surface-loaded them with trastuzumab to construct a multifunctional nanoprobe named Her-PEG-dMNPs. We used micro-PET/CT and PET/MRI multimodality imaging to evaluate the retention effect of the nanoprobe in HER2 expression in gastric cancer patient-derived xenograft (PDX) mice models after labeling of the radionuclides 64Cu or 124I and MRI contrast agent Mn2+. The nanoprobes can specifically target the HER2-expressing SKOV-3 cells in vitro (3.61 ± 0.74 vs. 1.24 ± 0.43 for 2 h, P = 0.002). In vivo, micro-PET/CT and PET/MRI showed that the 124I-labeled nanoprobe had greater contrast and retention effect in PDX models than unloaded dMNPs as carrier (1.63 ± 0.07 vs. 0.90 ± 0.04 at 24 h, P = 0.002), a similarity found in 64Cu-labeled Her-PEG-dMNPs. Because 124I has a longer half-life and matches the pharmacokinetics of the nanoparticles, we focused on the further evaluation of 124I-Her-PEG-dMNPs. Furthermore, immunohistochemistry staining confirmed the overexpression of HER2 in the animal model. This study developed and validated novel HER2-specific multimodality imaging nanoprobes for quantifying HER2 expression in mice. Through the strong retention effect of the tumor site, it can be used for the promotion of monoclonal antibody treatment effect and process monitoring.
研究领域:
肿瘤学
·
分子影像
·
纳米医学
·
癌症治疗
✓ 已验证
DOI
PubMed
高影响因子
BIOELECTROCHEMISTRY
·
2023
·
IF 5
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.
研究领域:
生物医学工程
·
分析化学
·
癌症研究
·
电化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2020
·Vol. 10
·期 1
·1-14
·
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.
研究领域:
癌症研究
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纳米技术
·
药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOPARTICLE RESEARCH
·
2013
·Vol. 15
·期 10
·1-10
·
IF 2.175
Li Jia,An Yan-Li,Zang Feng-Chao,Zong Shen-Fei,Cui Yi-Ping,Teng Gao-Jun
We report a composite nanoprobe based on silica-coated magnetic nanoparticles (NPs) for distinguishing breast cancers at different HER2 statuses. The nanoprobe has a core–shell structure, with Fe 3 O 4 NPs as the magnetic core and dye-embedded silica as the fluorescent shell, whose average size is about 150 nm. Besides, the outmost surfaces of the probes were modified with specific antibodies to endow the probe with a targeting ability. With such a structure, the nanoprobe can accomplish dual mode targeting of human breast cancer cells based on fluorescence and magnetic resonance imaging (MRI). In the experiments, three human breast cancer cell lines were used to test the targeting ability of the nanoprobe. Specifically, SKBR3 cells with a high HER2 expression level were used as the model target cells, while MCF7 cells with a lower HER2 expression levels and HER2-negative MDA-MB-231 cells were used as the controls. Both the fluorescence and MRI imaging results confirmed that the nanoprobe can distinguish three cancer cell lines with different HER2 expression levels. With the dual mode imaging and specific targeting properties, we anticipate that the presented nanoprobe may have a great potential in the diagnosis and treatment of cancerous diseases.
研究领域:
癌症研究
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纳米技术
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医学成像
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生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
MATERIALS & DESIGN
·
2022
·
IF 9.417
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.
研究领域:
药学
·
肿瘤学
·
纳米技术
·
生物医学工程
✓ 已验证
产品关联
DOI
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2024
·
IF 8
Huaze Shao,Hong Yan,Qing Tang,Shiquan Zheng,Hanren Chen,Lihong Liu
The overexpression of human epidermal growth factor receptor 2 (HER2) has been linked to aggressive breast cancer and worse clinical outcomes. However, accurately measuring HER2 remains challenging, due to its low serum content. Herein, we developed a novel method for HER2 detection in serum by the combination of aptamer with C-Ag + -C structure, Ag + -released hybridization chain reaction (Ag + -HCR) and coprecipitation of Ag + and gold nanoparticles (AuNPs) in the solution including Eosin Y (EY) and AgI colloids. Following the aptamer bound to HER2, signal amplification occurred through the release of numerous Ag + by Ag + -HCR. This process subsequently induced AuNPs aggregation on the surface of AgI colloids, resulting in reduced fluorescence intensity of EY in the supernatant. The reduced value of EY fluorescence intensity in the supernatant was proportional to the level of HER2. Under optimized reaction conditions, a wide detection range was obtained between 0.09 and 9000 pg/mL with a limit of detection of 11.7 fg/mL in diluted human serum, and 96 serum samples in a 96-well plate could be measured simultaneously by a microtiter plate reader within 2 h. Moreover, the quantitative results of HER2 were consistent with those obtained using the enzyme-linked immunosorbent assay kit ( r = 0.9995). Therefore, leveraging the delicate design of Ag + -HCR signal amplification, this enzyme-free, label-free, and effective method has demonstrated to be capable of detecting HER2 in serum due to its high sensitivity. Remarkably, this method may be extended to detect other cancer-related proteins and genes by replacing the corresponding target sequences.
研究领域:
生物化学
·
分子生物学
·
分析化学
·
癌症研究
✓ 已验证
DOI
高影响因子
ANALYTICA CHIMICA ACTA
·
2023
·
IF 6.2
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.
研究领域:
生物医学工程
·
分析化学
·
癌症研究
·
生物化学
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYST
·
2021
·Vol. 147
·期 5
·862-869
·
IF 4.616
Yawen Wu,Xiaolong Chen,Changjun Hou,Peng Lu,Lan Peng,Jiawei Li,Mei Yang,Danqun Huo
Human epidermal growth factor receptor 2 (HER2) is one of the specific markers of breast cancer, which is of great significance to the early diagnosis and prognosis of breast cancer. Here, a fluorescence biosensor was established to detect HER2 based on the fluorescence resonance energy transfer (FRET) and photoinduced electron transfer (PET) occurring between the bimetal-polydopamine organic framework with core–shell structure Au@PDA@UiO-66 and the Cy5 fluorophore in HER2-Cy5-Apt. Au@PDA@UiO-66 owns high-efficiency fluorescence quenching ability due to its large specific surface area and strong adsorption of single-stranded DNA. When the target appears, the fluorescence recovery space mediated by the target is large, so the proposed biosensor has better sensitivity in theory. Under optimized conditions, the proposed fluorescent biosensor can detect HER2 in a range of 0.005 ng mL−1 to 15 ng mL−1, with an actual detection limit as low as 0.005 ng mL−1. Corresponding selective experiments, reproducible experiments, and spiked experiments performed well, showing its great potential in HER2 detection.
研究领域:
生物医学工程
·
分析化学
·
癌症研究
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2021
·
IF 6.986
Wenqi Wang,Rui Han,Min Chen,Xiliang Luo
A facile strategy for the electrochemical detection of human epidermal growth factor receptor 2 (HER2), a breast cancer biomarker, was presented via the fabrication of an antifouling sensing interface based on the conducting polymer poly(3,4-ethylenedioxythiophene) (PEDOT) and a biocompatible peptide hydrogel. The peptide hydrogel prepared from a designed short peptide of Phe-Glu-Lys-Phe functionalized with a fluorene methoxycarbonyl group (Fmoc-FEKF) enabled excellent activity preservation for the immobilized biomolecules, and its good hydrophilicity facilitated effective alleviation of nonspecific adsorption or biofouling, while the PEDOT film provided a highly stable and conducting substrate. The developed biosensor was highly sensitive and selective for HER2 detection, with a wide linear response range from 0.1 ng mL–1 to 1.0 μg mL–1 and a low limit of detection of 45 pg mL–1. Moreover, the peptide hydrogel based biosensor was feasible to use for complex biological samples, and it was capable of detecting HER2 in human serum with clinically acceptable accuracy, manifesting a promising potential for practical application.
研究领域:
生物传感器
·
电化学
·
癌症诊断
·
生物医学工程
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-15
·
IF 10.6
Zhang Yue,Chen Shuyi,Ma Jie,Zhou Xiaobin,Sun Xinchen,Zhou Chenglin
An effective strategy for enzyme-enhanced electrochemical detection of human epidermal growth factor receptor 2 (HER2) is proposed for breast cancer diagnosis. This strategy utilizes a three-dimensional mesoporous covalent organic framework (COF), immobilized horseradish peroxidase (HRP), and a novel redox mediator, 4-acetamidophenol (APAP). The mesoporous structure, with encapsulation effect, and good biocompatibility of COF, makes the functionalized COF an efficient carrier for HRP immobilization (HRP-Ab-AuNPs@COF). It demonstrates superior catalytic activity, stability, and electrochemical performance compared to free HRP, thus making it an ideal probe for simultaneous target recognition and signal amplification. APAP is screened from four candidate phenolic compounds based on its high formal potential (0.32 V vs. Ag/AgCl), rapid electron transfer activity (k app = 2.80 × 10 5 M − 1 s − 1 ), excellent solubility and stability. These properties prove significantly better than the conventional mediator hydroquinone (HQ), achieving a higher signal-to-background ratio. By integrating decorated multi-walled carbon nanotubes as substrate materials, the electrochemical aptasensor achieves a low HER2 detection limit (0.418 pg mL − 1 ) with high specificity. This method’s selectivity surpasses that of the HQ-mediated method by 59–73%. Moreover, the aptasensor can effectively distinguish breast cancer patients and healthy individuals, as well as patients at different stages of the disease with high accuracy (AUC = 0.928). This performance exceeds traditional biomarkers CEA and CA15-3. This work paves novel avenues for innovative applications of COF-immobilized enzymes and the novel mediator APAP in electrochemical biosensing, thus holding significant promise for individualized breast cancer diagnosis and treatment.
研究领域:
生物医学工程
·
癌症诊断
·
电化学
·
纳米技术
·
生物传感器
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2019
·Vol. 7
·期 23
·3661-3669
·
IF 5.047
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.
研究领域:
生物医学工程
·
分析化学
·
纳米技术
·
癌症诊断
✓ 已验证
产品关联
DOI
高影响因子
ACS Applied Materials & Interfaces
·
2018
·
IF 8.097
Tingxizi Liang,Zhigang Yao,Jie Ding,Qianhao Min,Liping Jiang,Jun-Jie Zhu
Tumor-specific therapeutic platforms with improved targeting efficacy and minimized side effect are crucial in cancer therapy. Capitalizing on the recognition capability and biocompatibility of aptamers, we herein designed a multistage targeted drug-delivery system using multiple biodegradable molecules-enveloped nanovehicle that can be employed to efficiently treat human epithelial growth factor receptor (HER2)-overexpressing breast cancer. In this nanovehicle, two aptamers respectively specific to HER2 and ATP were organized in a hierarchical manner. The outmost HER2 aptamer (HB5) governs the recognition to HER2 protein overexpressed in SK-BR-3 cell lines, while the ATP aptamer incorporated with anticancer drug (−)-epigallocatechin gallate (EGCG) and protamine sulfate in the inner core functions as a switch of drug release in response to abundant intracellular ATP. The targeting and drug locker aptamers were cascaded for active targeting effect and stimuli responsiveness, guaranteeing the site-specific drug transportation and endogenous species-triggered drug release inside the tumor cells. Moreover, nanostructured lipid carriers (NLCs) were constructed to wrap and stabilize the loosely bounded ternary complex, minimizing premature drug leakage potentially encountered by the biomolecule assembled nanocarriers. This multiple biomolecules-enveloped nanovehicle demonstrated improved inhibitory actions on tumor growth and minimum side effect to normal organs and tissues both in vitro and in vivo. The presented nanovehicle built from recognition and therapeutic components in a nontoxic framework offered a promising drug-delivery platform with transport precision and biological safety.
研究领域:
癌症研究
·
药物递送系统
·
纳米技术
·
分子生物学
·
生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）