BIOCONJUGATE CHEMISTRY
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2020
·
IF 4.031
Yingshu Guo,Fei Liu,Yinhua Hu,Xiaofei Zheng,Xiuping Cao,Yanxi Zhu,Xiaoru Zhang,Dongjiao Li,Zhenhua Zhang,Si-kai Chen
Dark-field microscopy (DFM) based on localized surface plasmon resonance (LSPR) was used for observation of experimental phenomena, which is a hopeful nondamaging and non-photobleaching biological imaging technique. In this strategy, plasma nanoaggregates with stronger scattering efficiency were formed in the presence of the target, causing a “turn-on” phenomenon, when asymmetry modified AuNPs were introduced as probes with zero LSPR background. First, Au1–N3 probe and Au2–C≡C probe were designed for the cycloaddition between azide and alkyne to form AuNP dimers under catalytic action by Cu+, which was obtained from the reduction of Cu2+ by sodium ascorbate. The two kinds of probes were successfully used for the detection of Cu2+ in rat serum. Then, to apply this concept to protein on cells, DNA and antibody were modified on the probes. DNA1/Au1–N3 probe and anti-HER2/Au2–C≡C probe were proposed for HER2 protein DFM on cells. By designing an aptamer sequence in primer, the rolling circle amplification (RCA) was introduced in HER2 DFM on cells, and the image signal was much brighter than that from no-RCA. The unique design made it easier to discriminate the target signal from background noise in cell DFM. This method might be used in the fields of molecular diagnostics and cell imaging.
研究领域:
生物化学
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分子生物学
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医学影像学
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产品关联
DOI
PubMed
高影响因子
Theranostics
·
2015
·
IF 8.022
Li Ding,Caiping Tian,Song Feng,Guissi Fida,Congying Zhang,Yuxiang Ma,Guanhua Ai,Samuel Achilefu,Yueqing Gu
Targeting tumors using miniature antibodies is a novel and attractive therapeutic approach, as these biomolecules exhibit low immunogenicity, rapid clearance, and high targeting specificity. However, most of the small-sized antibodies in existence do not exhibit marked anti-tumor effects, which limit their use in targeted cancer immunotherapy. To overcome this difficulty in targeting multiple biomarkers by combination therapies, we designed a new bifunctional antibody, named MaAbNA (multivalent antibody comprised of nanobody and affibody moieties), capable of targeting EGFR1 and HER2, which are widely overexpressed in a variety of tumor types. The small-sized (29 kDa) MaAbNA, which was expressed in E.coli , consists of one anti-EGFR1 nanobody and two anti-HER2 affibodies, and possesses high affinity (K D ) for EGFR1 (~4.1 nM) and HER2 (~4.7 nM). In order to enhance its anti-tumor activity, MaAbNA was conjugated with adriamycin (ADM) using a PEG2000 linker, forming a new complex anticancer drug, MaAbNA-PEG2000-ADM. MaAbNA exhibited high inhibitory effects on tumor cells over-expressing both EGFR1 and HER2, but displayed minimal cytotoxicity in cells expressing low levels of EGFR1 and HER2. Moreover, MaAbNA-PEG2000-ADM displayed increased tumoricidal effects than ADM or MaAbNA alone, as well exhibited greater antitumor efficacy than EGFR1 (Cetuximab) and HER2 (Herceptin) antibody drugs. The ability of MaAbNA to regulate expression of downstream oncogenes c-jun, c-fos, c-myc, as well as AEG-1 for therapeutic potential was evaluated by qPCR and western-blot analyses. The antitumor efficacy of MaAbNA and its derivative MaAbNA-PEG2000-ADM were validated in vivo , highlighting the potential for use of MaAbNA as a highly tumor-specific dual molecular imaging probe and targeted cancer therapeutic.
研究领域:
肿瘤学
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药理学
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生物技术
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Drug Design Development and Therapy
·
2022
·
IF 4.319
Keying Liang,Shengsheng Mei,Xiangzheng Gao,Shanshan Peng,Jinbiao Zhan
Purpose T-DM1 is an antibody–drug conjugate (ADC) consisting of trastuzumab and DM1 linked together. T-DM1 binds to human epidermal growth factor receptor-2 (HER2) in tumors and then triggers the endocytosis of T-DM1 and release of payload. Therefore, endocytosis efficacy is considered as a critical step for the initiation of T-DM1 therapy; however, the endocytosis mechanism of T-DM1 remains poorly understood. Meanwhile, HER2 is regarded as an internalization-resistant receptor, which hinders the endocytosis and effectiveness of T-DM1. The present study is to explore the T-DM1 endocytosis pathway, which may provide insights into the internalization mechanism of ADCs and help to improve efficacy.Methods Confocal microscopy and flow cytometry were used to analyse T-DM1 intracellular trafficking and endocytosis efficiency, while Western blot assay was performed to detect T-DM1 degradation.Results We found that intracellular T-DM1 was increased to 50% within 12 h. T-DM1 was colocalized with cholera toxin B (CTxB), a lipid raft marker, within 2 h and then degraded in lysosome. Upon overexpression of caveolin-1 (CAV-1) and utilization of caveolae/lipid-raft disruptors, we found that temporal CAV-1 upregulation significantly facilitated T-DM1 endocytosis and degradation, whereas nystatin and lovastatin disrupted caveolae/lipid-raft structure and inhibited T-DM1 degradation. We demonstrate that T-DM1 internalizes through the lipid raft-mediated endocytosis in a CAV-1 dependent manner, rather than through the clathrin-mediated endocytosis in HER2-positive cancer cells.Conclusion Our findings suggest that modulation of the caveolae/lipid-raft mediated endocytosis may be a possible option for improving the clinical therapeutic effect of T-DM1 because it plays a key role in regulating T-DM1 internalization.
研究领域:
肿瘤学
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细胞生物学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
Nanoscale Research Letters
·
2014
·Vol. 9
·期 1
·1-13
·
IF 2.481
Li Chao,Ji Yang,Wang Can,Liang Shujing,Pan Fei,Zhang Chunlei,Chen Feng,Fu Hualin,Wang Kan,Cui Daxiang
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.
研究领域:
生物医学工程
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纳米医学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2023
·
IF 5.9
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.
研究领域:
生物医学工程
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分析化学
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肿瘤学
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产品关联
DOI
高影响因子
OPTICS EXPRESS
·
2022
·Vol. 30
·期 20
·36839-36848
·
IF 3.833
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.
研究领域:
生物医学工程
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分子生物学
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光学传感
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产品关联
DOI
PubMed
高影响因子
MICROCHIMICA ACTA
·
2023
·Vol. 190
·期 2
·1-9
·
IF 5.7
Du Chunyang,Jiao Jiao,Zhang Hongfang
A nanochannel-based electrochemical immunoassay was developed for the detection of human epidermal growth factor receptor 2 (HER2), with molybdate as the reporter to explore the interaction occurring into the nanochannels. The presence of target increased steric hindrance of the antibody-functionalized nanochannels, thereby hindering the transport of molybdate. And the reporter could be monitored by working electrode modified with hydroxyapatite nanoparticles, based on the formation of the redox-active molybdophosphate. As a result, peak current obtained at ca. − 0.28 V in square wave voltammograms could be applied to quantitative determination of HER2. The electrochemical signal increased linearly with the logarithm of the concentration of HER2 in a broad dynamic range of 0.1 pg∙mL −1 to 10 ng∙mL −1 with a detection limit of 0.05 pg∙mL −1 . The reliability of this immunoassay was validated by a recovery range of 99.5% to 111.7% for the detection of three different levels of HER2 in human serum samples. Integrating with multiple bionanochannels, this immunoassay is expected to provide a versatile approach for quantitative detection of various biomarkers in related disease diagnosis and therapy. Graphical Abstract
研究领域:
纳米技术
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生物医学工程
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分析化学
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癌症诊断
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产品关联
DOI
PubMed
高影响因子
ANALYTICAL CHEMISTRY
·
2022
·
IF 8.008
Yangcenzi Xie,Yu Wen,Xiaoming Su,Chao Zheng,Ming Li
The expression of human epidermal growth factor receptor-2 (HER2) has important implications for pathogenesis, progression, and therapeutic efficacy of breast cancer. The detection of its variation during the treatment is crucial for therapeutic decision-making but remains a grand challenge, especially at the cellular level. Here, we develop a machine learning-driven surface-enhanced Raman spectroscopy (SERS)-integrated strategy for label-free detection of cellular HER2. Specifically, our method allows the extraction of cell-rich spectral signatures utilized for identification and classification of cancer cells with distinct HER2 expression with a high accuracy of 99.6%. By combining label-free SERS detection and machine learning-driven chemometric analysis, we are able to perform longitudinal monitoring of therapeutic efficacy at the cellular level during the treatment of HER2+ breast cancer, which aids in the subsequent decision-making and management. This work provides a promising technique capable of performing dynamic label-free spectroscopic detection for therapeutic surveillance of diseases.
研究领域:
癌症生物学
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生物医学工程
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光谱学
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机器学习
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治疗监测
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产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES A-PHYSICOCHEMICAL AND ENGINEERING ASPECTS
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2025
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IF 5.4
Aimei Li,Xue Tian,Feihu Hu,Chuntao Li,Ziru Liu,Chunbo Lu,Xizhen Wang,Yingshuai Wang,Lingling Dai,Baolong Zhou,Jingkun Bai
High expression of human epidermal growth factor receptor 2 (HER2) accelerates the proliferation of breast cancer cells and the progression and malignancy of breast cancer. HER2-positive breast cancer cells often overexpress antiapoptotic proteins, enabling them to resist apoptosis despite the presence of proapoptotic signals. Additionally, traditional chemotherapeutic drugs are easily eliminated from tumor cells, preventing them from reaching concentrations adequate for effectively destroying tumors or inhibiting tumor growth. In this research, these obstacles were addressed by developing a drug delivery system based on the amphipathic peptide Pep1. The model chemotherapeutic drugs doxorubicin (DOX) and curcumin (CUR) are encapsulated by Pep1 (DC/Pep1) to form spherical nanoparticles, which are ultimately converted to nanofibers by alkaline phosphatase (ALP) to increase drug accumulation in SKBR3 cells. Compared with DC/Pep2, which cannot undergo a morphological transformation, DC/Pep1 increases the expression of E-cadherin and pro-Caspase-3 and inhibits the migration and accelerates the apoptosis of HER2-positive breast cancer cells. Morphologically transformable amphipathic peptides, as drug carriers that target HER2-positive breast cancer cells, represent a facile and promising strategy for breast cancer therapy.
研究领域:
肿瘤学
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药学
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生物材料学
✓ 已验证
DOI
高影响因子
ANALYTICAL CHEMISTRY
·
2024
·
IF 6.7
Qianxi Zhou,Yuying Pan,Qizhi Liang,Jiahua Yang,Sha Zhu,Hai Shi,Genxi Li
Peptide-engineered nanoparticles have great potential for biomedical research and application. In this work, we have designed and fabricated an electrochemical biosensor based on peptide-guided assembly of silver nanoparticles (AgNPs), in which a peptide is endowed with dual functions to recognize target and guide assembly of AgNPs. As a proof of concept, the performance of this biosensor is validated by quantifying human epidermal growth factor receptor 2 (HER2) protein. In detail, the end of the HER2-specific binding peptide is grafted with a positively charged peptide, which can guide the orderly assembly of AgNPs, while electrochemical signals can be obtained through phosphine-silver coordination. Using this electrochemical biosensor, HER2 protein can be quantified with high sensitivity and specificity, and the limit of detection can be as low as 0.05 pg/mL. Moreover, the antifouling electrode surface prepared by the modification of a layer of antifouling zwitterionic peptide allows this biosensor to be used for the detection of serum HER2 protein from breast cancer patients, which provides the clear evidence for the distinction of HER2+ breast cancer patients and HER2- breast cancer patients.
研究领域:
生物医学工程
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纳米技术
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癌症诊断
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2021
·Vol. 19
·期 1
·1-23
·
IF 10.435
Wang Haijun,Jia Dianlong,Yuan Dandan,Yin Xiaolei,Yuan Fengjiao,Wang Feifei,Shi Wenna,Li Hui,Zhu Li-Min,Fan Qing
Background Solid tumor hypoxic conditions prevent the generation of reactive oxygen species (ROS) and the formation of DNA double-strand breaks (DSBs) induced by ionizing radiation, which ultimately contributes to radiotherapy (RT) resistance. Recently, there have been significant technical advances in nanomedicine to reduce hypoxia by facilitating in situ O 2 production, which in turn serves as a “radiosensitizer” to increase the sensitivity of tumor cells to ionizing radiation. However, off-target damage to the tumor-surrounding healthy tissue by high-energy radiation is often unavoidable, and tumor cells that are further away from the focal point of ionizing radiation may avoid damage. Therefore, there is an urgent need to develop an intelligent targeted nanoplatform to enable precise enhanced RT-induced DNA damage and combined therapy. Results Human epidermal growth factor receptor 2 (Her2)-specific dimeric affibody (Z Her2 ) mediated cisplatin-loaded mesoporous polydopamine/MnO 2 /polydopamine nanoparticles (Pt@mPDA/MnO 2 /PDA-Z Her2 NPs) for MRI and enhanced chemo-radiotherapy of Her2-positive ovarian tumors is reported. These NPs are biodegradable under a simulated tumor microenvironment, resulting in accelerated cisplatin release, as well as localized production of O 2 . Z Her2 , produced using the E. coli expression system, endowed NPs with Her2-dependent binding ability in Her2-positive SKOV-3 cells. An in vivo MRI revealed obvious T 1 contrast enhancement at the tumor site. Moreover, these NPs achieved efficient tumor homing and penetration via the efficient internalization and penetrability of Z Her2 . These NPs exhibited excellent inhibition of tumor growth with X-ray irradiation. An immunofluorescence assay showed that these NPs significantly reduced the expression of HIF-1α and improved ROS levels, resulting in radiosensitization. Conclusions The nanocarriers described in the present study integrated Her2 targeting, diagnosis and RT sensitization into a single platform, thus providing a novel approach for translational tumor theranostics. Graphic abstract
研究领域:
纳米医学
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癌症治疗
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分子生物学
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生物医学工程
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放射生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
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2015
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IF 6.025
Kaiyuan Wang,Hui Yao,Ying Meng,Yi Wang,Xueying Yan,Rongqin Huang
Tumor-specific therapeutic platforms designed for combined tumor therapy has recently received wide attention. In this work, a new HB5 aptamer-functionalized mesoporous silica–carbon based doxorubicin (DOX)-loaded system (MSCN-PEG-HB5/DOX) was successfully constructed and characterized for chemo-photothermal combined therapy of human epithelial growth factor receptor 2 (HER2)-positive breast cancer cells. The in vitro release result showed that MSCN-PEG-HB5/DOX exhibited pH-sensitive and NIR-triggered release manner. HB5-modified nanoparticles showed significant higher cellular uptake in HER2-positive breast cancer cells (SK-BR-3) but not in normal breast epithelial cells (MCF-10A), compared to unmodified counterparts. The intracellular uptake of functional nanoparticles was mainly based on the receptor-mediated mechanism which was energy-dependent. Cytotoxicity experiments demonstrated that combined therapy induced highest cell killing effect compared to chemotherapy and photothermal therapy alone. The combination index (CI) was 0.253 indicating the synergistic effect of chemotherapy and photothermal therapy. These findings suggested that MSCN-PEG-HB5/DOX was a potential chemo-photothermal therapeutic platform targeting to HER2-positive breast cancers.
研究领域:
肿瘤学
·
纳米医学
·
药剂学
✓ 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）