ANALYTICAL CHEMISTRY
·
2021
·
IF 6.986
Han Liu,Wangwang Zheng,Yuan Zhao,Yuanzhen Zhou
An electrochemical sensing interface is limited by poor reproducibility and inevitable interferences present in practical applications due to the weak electrochemical signals of nanotags. This motivates the need for effective strategies to enhance the electroactivity performances of nanotags. In this contribution, a plasmon-enhanced electroactivity mechanism is proposed for AuRu-based nanostructures under illumination and applied for accurate detection of human epidermal growth factor receptor-2 (HER2). AuRu nanoparticles (NPs) harvested light energy through plasmon excitation and generated holes to participate in the electrooxidation process. The production of holes resulted in the electrooxidation signal enhancement of AuRu NPs. AuRu NPs were assembled with Au NPs using HER2 aptamers as linkers, and the plasmonic coupling between AuRu NPs and Au NPs produced an intense electromagnetic field, which further enhanced the electrooxidation signals of AuRu NPs. An AuRu–Au NP assembly-dependent electrochemical aptasensor was established for the accurate detection of HER2, and the limit of detection (LOD) was as low as 1.7 pg/mL. The plasmon-enhanced electroactivity mechanism endowed AuRu-based nanostructures with strong and noninterfering electrochemical signals for sensitive and accurate detection. This insight opens new horizons for the construction of desired electroactive nanostructures for electroanalysis applications.
研究领域:
生物传感
·
纳米医学
·
电分析化学
✓ 已验证
DOI
PubMed
高影响因子
ACS Nano
·
2023
·
IF 17.1
Xiaoming Su,Xinyu Liu,Yangcenzi Xie,Mingyang Chen,Chao Zheng,Hong Zhong,Ming Li
Protein profiles of exosomes (EXOs) in clinical samples of cancer patients have become a promising diagnostic and therapeutic biomarker. However, simultaneous quantitative analysis of multiple exosomal proteins of interest remains challenging. To address the unmet need, we develop a paper-based surface-enhanced Raman spectroscopy (SERS)-vertical flow biosensor, named iREX (integrated Raman spectroscopic EXO) biosensor, for multiplexed quantitative profiling of exosomal proteins in clinical serum samples of patients. Utilizing this iREX biosensor, we are able to quantitatively profile MUC1, HER2 and CEA in EXO samples derived from various breast cancer cell subtypes. The results show discriminative expression profiles of the three exosomal proteins in these cell subtypes, which allows for accurate diagnosis and molecular subtyping of breast cancer. We further validate the clinical utility of the iREX biosensor for simultaneous quantitative analysis of MUC1, HER2 and CEA in patient’s blood serums, thereby aiding in noninvasive breast cancer subtyping and longitudinal treatment monitoring. Our iREX biosensor integrating the SERS detection in a vertical flow diagnostic device offers great advantages of high sensitivity, molecular specificity, powerful multiplexing capability, and high diagnostic accuracy. We believe that the iREX biosensor could be a promising clinical tool for comprehensive analysis of exosomal proteins in clinical samples for personalized diagnosis and precise management of breast cancer.
研究领域:
生物医学工程
·
肿瘤学
·
诊断学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Nanoscale
·
2017
·Vol. 9
·期 35
·13142-13152
·
IF 7.367
Jingxin Mo,Li Wang,Xiaojia Huang,Bing Lu,Changye Zou,Lili Wei,Junjun Chu,Paul K. Eggers,Shen Chen,Colin L. Raston,Jun Wu,Lee Yong Lim,Wei Zhao
Ovarian cancer (OC) is the most lethal gynecologic cancer. Survival statistics have show no significant developments over the last three decades, highlighting the fact that current therapeutic strategies require substantial improvements. In this study, we designed a novel folic acid-PEG-conjugated p-phosphonated calix[4]arene nanoparticle (Fp-PCN) for the simultaneous delivery of paclitaxel (PAC) and carboplatin (CAR) at an optimal ratio (5 : 1, mol : mol) to utilize their potential synergistic effect against OC cells. The Fp-PCNs loaded with PAC and CAR (Fp-PCNPAC+CAR) resulted in a remarkable efficacy in the suppression of OC, both in vitro and in vivo. Compared to free drugs, Fp-PCNPAC+CAR showed stronger apoptosis induction as well as invasion and self-renewal capacity suppression in SKOV-3 cells. The molecular mechanism to address the synergism is that Fp-PCNPAC+CAR downregulated JMJD3 expression to modulate the H3K27me3 epigenetic mark of the promoters of HER2 and MYCN. Furthermore, the expressions of JMJD3 and HER2 were significantly associated with poor outcomes for ovarian patients. Our study demonstrates that co-delivery of PAC and CAR can be achieved with the Fp-PCNs, and reveals a previously unrecognized and unexpected role of the JMJD3-HER2 signaling axis in PAC and CAR treatment of OC.
研究领域:
肿瘤学
·
药学
·
纳米技术
·
分子生物学
·
癌症治疗
✓ 已验证
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Chao Zhang,Mengnan Han,Fanghua Zhang,Xueli Yang,Jie Du,Honglei Zhang,Wei Li,Shengxi Chen
Background Chemotherapy, as an adjuvant treatment strategy for HER2-positive breast cancer, can effectively improve clinical symptoms and overcome the drug resistance of therapeutic monoclonal antibodies. Nucleoside analogues are a class of traditional chemotherapeutic drugs that are widely applied in adjuvant therapy. However, there are many critical issues that limit their clinical efficiency, including poor selectivity and stability, severe side effects and suboptimal therapeutic efficacy. Hence, this work aims to develop a new DNA nanocarrier for targeted drug delivery to solve the above problems.Methods Four 41-mer DNA strands were synthesized and 10 FUdR molecules were attached to 5ʹ end of each DNA strand by DNA solid-phase synthesis. An affibody molecule was connected to the end of polymeric FUdR through a linker in one of the four strands. The affibody-FUdR-tetrahedral DNA nanostructures (affi-F/TDNs) were self-assembled through four DNA strands, in which one vertex was connected to an affibody at the end of a polymeric FUdR tail and three vertices were only polymeric FUdR tails. In vitro cellular uptake of affi-F/TDNs was examined visually with confocal fluorescence microscopy and flow cytometry, and the cytotoxicity of affi-F/TDNs against cancer cells was investigated with MTT assay. Cell apoptosis was detected by Annexin V-FITC/PI double staining method. Using NOD/SCID (Mus Musculus) mice model, the targeted killing efficacy of affi-F/TDNs was also evaluated.Results The drug-loading of FUdR in affi-TDNs was 19.6% in mole ratio. The in vitro results showed that affi-F/TDNs had high selectivity and inhibition (81.2%) for breast cancer BT474 cells overexpressing HER2 and low toxicity in MCF-7 cells with low HER2 expression. During the in vivo application, affi-F/TDNs displayed good stability in the blood circulation, achieved specific accumulation in tumor region and the best antitumor efficacy (inhibition ratio of 58.1%), and showed excellent biocompatibility.Conclusions The affibody-DNA tetrahedrons, as a simple and effective active targeting delivery nanocarrier, provided a new avenue for the transport of nucleoside antitumor drugs.
研究领域:
肿瘤学
·
药学
·
纳米技术
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2026
·
IF 12.4
Yubei Duan,Jiaxin Huang,Tianping Huang,Kaige Yang,Liwen Qi,Baohua Yu,Fanping Li,Maosheng Yin,Lei Zhao,Zhenghua Chai,Weihua Liang,Haijun Zhang,Jing Fei,Jinsong Ding,Chenghua Luo,Wenhu Zhou,Jianming Hu
HER2-positive breast cancer is characterized by aggressive proliferation, high metastatic potential, and immune evasion, yet current HER2-targeted therapies are hindered by resistance and immunosuppressive microenvironments. Here, we report a multifunctional nanoplatform (TanDNA@MnO 2 ) constructed by biomineralizing manganese dioxide with a tandem DNA (TanDNA) that integrates a HER2-targeting DNAzyme for gene silencing and a dsDNA motif for cGAS–STING activation. TanDNA@MnO 2 exhibited favorable colloidal stability, tumor accumulation, and pH/GSH-responsive Mn 2+ release. Mn 2+ served both as a cofactor to enhance DNAzyme catalytic activity and as an immune agonist to stimulate cGAS–STING signaling. Mechanistic studies revealed dual functionality: HER2 silencing directly inhibited oncogenic proliferation and relieved HER2-mediated suppression of cGAS–STING, while dsDNA and Mn 2+ synergistically amplified STING–TBK1–IRF3 activation. Consequently, TanDNA@MnO 2 remodeled the tumor immune microenvironment by promoting M1 macrophage polarization, dendritic cell maturation, and CD8 + T cell infiltration, accompanied by increased production of anti-tumor cytokines and chemokines. In vivo, TanDNA@MnO 2 achieved potent tumor growth inhibition with negligible systemic toxicity, underscoring its promise as a generalizable nucleic acid–metal oxide nanoplatform that combines gene silencing with immunotherapy to overcome resistance and immune evasion in HER2-positive breast cancer.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2026
·
IF 14.1
Jiaying Zheng,Yi Zhu,Xinrui Li,Sunxian Dai,Xiangyuan Ma,Hongwei Lu,Zhongling Wang,Benqing Zhou
Breast cancer continues to be a leading cause of cancer‐related mortality in women globally, where precise diagnosis and clear tumor demarcation are critical for effective treatment. Herein, we developed a strategic platform that combines a novel ultrasensitive magnetic resonance (MR) contrast agent with deep learning to significantly enhance the tumor‐to‐normal ratio (TNR). We designed ultrasmall iron oxide nanoparticles (USIO NPs) conjugated with trastuzumab (Tmab) for targeted MR imaging of HER2‐positive breast cancer. The USIO@Tmab nanoprobe demonstrated excellent HER2 specificity and pH‐responsive activation. The relaxivity of the nanoprobe shifted from a low T 1 ‐weighted intensity (r 1 = 1.43 mM − 1 s − 1 ) under physiological conditions to an enhanced value (r 1 = 4.07 mM − 1 s − 1 ) in the acidic tumor microenvironment due to the detachment of Tmab protein. Additionally, we employed the 3D nnU‐Net deep learning framework as a post‐processing visualization aid to enhance tumor boundary detection via image fusion, rather than to amplify the underlying MRI signal. This approach yielded high segmentation accuracy, with an Intersection‐over‐Union (IoU) of 0.88 and a Dice coefficient of 0.93. This strategy provided an additional 2.59‐fold increase in TNR and enabled the reconstruction of three‐dimensional (3D) tumor models, offering clinicians an intuitive visualization of tumor structure for precise diagnosis and surgical guidance. A novel targeted and pH‐responsive MRI contrast agent was integrated with a 3D nnU‐Net deep learning framework to enable accurate delineation of tumor boundary morphology in HER2‐positive breast cancer imaging.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
·
2025
·
IF 6.8
Zuojie Li,Lina Diao,Peiwen Han,Qingna Xiao,Dajie Ding,Junhong Feng,Jianyong Jiang,Junbo Zhang
Radiolabeled human epidermal growth factor receptor 2 (HER2) tracers are important tools for the accurate clinical diagnosis and treatment of HER2-positive tumors. The aim of this study was to investigate the potential of small molecule inhibitors (lapatinib) as target groups for novel radiotracers targeting HER2. Twelve stable radiotracers were prepared by chelation with different coligands. The relationships between the linker and the combination of coligands with pharmacodynamics were systematically evaluated. [99mTc]Tc-Lapa-HYNIC-TPPTS exhibits the most favorable pharmacokinetic properties, as it can stably bind to the active pocket of the HER2 protein. Both in vitro and in vivo studies demonstrated its high targeting specificity toward HER2. SPECT images of [99mTc]Tc-Lapa-HYNIC-TPPTS in HER2-positive model mice revealed that it can effectively locate tumors. This study is the first attempt at a 99mTc-labeled small-molecule inhibitor tracer targeting HER2, showing great potential for applications in the diagnosis of HER2-positive cancers.
✓ 已验证
DOI
PubMed
高影响因子
Journal of Extracellular Vesicles
·
2023
·Vol. 12
·期 9
·12364
·
IF 16
Jie He,Hengyu Li,John Mai,Yuqing Ke,Chunhui Zhai,Jiao Jiao Li,Lai Jiang,Guangxia Shen,Xianting Ding
Extracellular vesicle (EV) surface proteins, expressed by primary tumours, are important biomarkers for early cancer diagnosis. However, the detection of these EV proteins is complicated by their low abundance and interference from non-EV components in clinical samples. Herein, we present a MEmbrane-Specific Separation and two-step Cascade AmpLificatioN (MESS2CAN) strategy for direct detection of EV surface proteins within 4 h. MESS2CAN utilises novel lipid probes (long chains linked by PEG2K with biotin at one end, and DSPE at the other end) and streptavidin-coated magnetic beads, permitting a 49.6% EV recovery rate within 1 h. A dual amplification strategy with a primer exchange reaction (PER) cascaded by the Cas12a system then allows sensitive detection of the target protein at 10 EV particles per microliter. Using 4 cell lines and 90 clinical test samples, we demonstrate MESS2CAN for analysing HER2, EpCAM and EGFR expression on EVs derived from cells and patient plasma. MESS2CAN reports the desired specificity and sensitivity of EGFR (AUC = 0.98) and of HER2 (AUC = 1) for discriminating between HER2-positive breast cancer, triple-negative breast cancer and healthy donors. MESS2CAN is a pioneering method for highly sensitive in vitro EV diagnostics, applicable to clinical samples with trace amounts of EVs.
研究领域:
生物技术
·
医学诊断
·
癌症研究
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2018
·
IF 5.123
Hong Xing,Tianxiang Wei,Xin Lin,Zhihui Dai
An enhanced near-infrared (NIR) FRET biosensing system based on the novel donor-acceptor pair (MnCuInS/ [email protected] and urchin-like Au NPs) was developed for the sensitive detection of HER2 protein. In this strategy, MnCuInS/ZnS quantum dots (QDs) were chosen due to their NIR emission, high quantum efficiency , and low toxicity. Amounts of MnCuInS/ZnS QDs were encapsulated in BSA to form MnCuInS/ [email protected] nanoparticles, which can easily transfer MnCuInS/ZnS QDs from organic phase into aqueous solution, and the formed nanoparticles were applied as the energy donor which significantly enhanced the fluorescence intensity . As for the energy acceptor, urchin-like Au nanoparticles (Au NPs) with novel structure, good stability and excellent quenching ability towards NIR fluorescence were selected. Thus, the NIR MnCuInS/ [email protected] and urchin-like Au NPs were designed as a novel donor-acceptor pair for FRET assay. By combining the optical advantages of NIR QDs encapsulated BSA nanoparticles with the excellent fluorescence quenching ability of urchin-like Au NPs, the proposed FRET-based biosensor realized enhanced FRET effect for highly sensitive detection of HER2 in human serum samples. A wide detection range (2–100 ng mL −1 ) and a low detection limit (1 ng mL −1 ) were obtained. This sensing system can decrease the interference of other biomolecules in NIR region, can be applied to other biomarker determination in vitro, and also shows great potential for in vivo diagnosis.
研究领域:
生物传感
·
医学检测
·
纳米材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
·
2026
·
IF 2.9
Guodong Shen,Ting Zhao,Yi Shen,Yimin Zhu,Yuxin Mei,Xiaoyan Yang,Lian Lian
The clinical efficacy of docetaxel (DTX) in treating HER2-positive breast cancer is hampered by poor solubility and systemic toxicity, while metformin (Met) shows anti-cancer potential by targeting tumor metabolism. We hypothesized that a biomimetic nanoplatform co-delivering DTX and Met could achieve synergistic anti-tumor effects with enhanced safety. This study developed tumor cell membrane-camouflaged mesoporous silica nanoparticles co-loaded with DTX and Met (mem(DTX&Met@MSNs)). The nanoparticles were characterized for particle size, stability, drug loading, and membrane coating. In vitro assays were conducted to assess cellular uptake, cytotoxicity, and synergistic effects. In vivo studies were performed in HER2-positive breast cancer-bearing mice to evaluate biodistribution, anti-tumor efficacy, toxicity, and histopathology. The mem(DTX&Met@MSNs) nanoparticles showed a core-shell structure and pH-responsive release, with over 80% drug release at pH 6.5 versus less than 40% at pH 7.4. Biomimetic coating enabled homologous targeting, enhancing cellular uptake and synergistic cytotoxicity in SK-BR-3 cells (7.89% apoptosis). In vivo, the system prolonged the circulation half-life to nearly 6 h, effectively suppressed tumor growth, and demonstrated excellent biocompatibility with no significant toxicity or body weight loss. In conclusion, mem(DTX&Met@MSNs) integrates homologous targeting with dual-drug synergism, offering a safe and effective strategy for the treatment of HER2-positive breast cancer.
✓ 已验证
DOI
PubMed
高影响因子
BIOTECHNOLOGY AND APPLIED BIOCHEMISTRY
·
2025
·
IF 2.7
Weibin Luo,Zhengyuan Yang,Shihua Gao,Bin Peng
Lung carcinoma is one of the most severe types of cancer, characterized by a dismal prognosis and low overall survival rate, primarily due to late diagnosis and the ineffectiveness of standard treatments. Hence, this study aimed to develop bevacizumab (BZ)-functionalized albumin (BS)-clad, carboplatin (CP)-loaded hollow mesoporous selenium (HMS) nanoparticles (BBHMSC) for the targeted administration of HER2+ Calu-3 lung cancer. The structural properties of these nanoparticles were characterized using transmission electron microscopy (TEM). Cell viability was assessed using the 3-[4,5-dimethylthiazol-2-yl]- 2,5-diphenyltetrazolium bromide (MTT) assay. The images were obtained from fluorescence microscopy. The in vitro characterization of the pharmacological characteristics indicated that BBHMSC was uniformly disseminated, with a particle size of 171.52 ± 4.3 nm. In vitro release tests demonstrated that BBHMSC proficiently regulated the release of CP in the tumor microenvironment (elevated glutathione concentration), achieving a cumulative release rate of 87.1 ± 3.9% over 48 h. A cellular uptake assay validated that BBHMSC has an effective tumor-targeting capability. In vitro cell investigations, MTT studies, have shown that BBHMSC dramatically suppresses proliferation and growth. Further, BBHMSC enhances the apoptosis of HER2+ Calu-3 cells by fluorescence and flow cytometry methods. The data indicate that BBHMSC may be an effective targeted therapy for HER2+ti lung cancer.
研究领域:
肿瘤学
·
药剂学
·
生物医学工程
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TALANTA
·
2023
·
IF 6.1
Chen Qing,Xiao-nan Zhang,Guo-yu Ding,Yu-fei Ma,Ming-sheng Zhou,Yang Zhang
In this study, we designed and prepared a trastuzumab-coupled drug delivery system with pH response characteristics using mesoporous zeolitic imidazolate framework-8 (ZIF-8) as the carrier, Trastuzumab@ZIF-8@DOX. As results, the targeted drug delivery system (TDDS) ultimately showed high drug loading and good biocompatibility. The cumulative curve of drug release indicated that the early leakage levels were low under neutral pH conditions. However, under acidic pH conditions, there was an effective enhancement in drug release, indicating the presence of an explicit pH-triggered drug release mechanism. The results indicate that the prepared nanoparticles have the potential to serve as drug delivery systems, as they can release the loaded drug in a controlled manner. The results of cellular uptake tests showed that the uptake of the nanoparticles was greatly enhanced by the internalization mediated by the HER2 antibody. This finding indicates that the prepared nanoparticles can selectively target cancer cells that overexpress HER2. When the doxorubicin dose was 5 μg/ml, the survival rate of SK-BR-3 cells (cancer cells) was 47.75 %, and the survival rate of HaCaT cells (healthy cells) was 75.25 % when co-cultured with both cells. The therapeutic efficacy of Trastuzumab@ZIF-8@DOX was assessed on BALB/c nude mice to validate its potential as an effective drug delivery system for tumor inhibition in vivo. In conclusion, these findings demonstrate the specificity-targeted and pH-responsive nature of this smart drug delivery system, highlighting its promising prospects for efficient and controllable cancer treatment applications.
✓ 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）