Frontiers in Pharmacology
·
2022
·
IF 5.988
Ming Ying,Qin Li,Jingbo Wu,Yihang Jiang,Zhourui Xu,Mingze Ma,Gaixia Xu
Breast cancer is characterized by the uncontrolled proliferation of breast epithelial cells under the action of a variety of carcinogens. Although HER2-inhibitors were currently applied for HER2-positive breast cancer patients, they didn’t work for patients with resistance to HER2-targeted anti-cancer drugs. In this work, we prepared novel CuS@BSA-NB2 nanoparticles (NPs) for breast cancer photothermal therapy (PTT). The NPs had good biocompatibility due to the Bovine Serum Albumin (BSA) encapsulating and excellent targeting to HER2 because of nanobody 2 (NB2). Under 808 nm laser irradiation, CuS@BSA-NB2 NPs had high photothermal conversion efficiency and photothermal stability. Meanwhile, we constructed a stable cell line of MDA-MB-231/HER2 with a high expression of HER2 protein. Immunofluorescence and ICP-MS assays showed that CuS@BSA-NB2 NPs can be specifically enriched and be ingested in MDA-MB-231/HER2 cells. Furthermore, CuS@BSA-NB2 NPs had shown a more significant photothermal treatment effect than CuS@BSA under certain treatment conditions for MDA-MB-231/HER2. In addition, the cytotoxicity assay demonstrated that CuS@BSA-NB2 NPs had a low toxicity for MDA-MB-231/HER2 cells. The above results suggested that CuS@BSA-NB2 NPs were great photothermal therapeutic agents to reduce the malignant proliferation of breast epithelial cells and have potential for breast cancer therapy.Keywords: CuS@BSA-NB2 nanoparticles, photothermal therapy, HER2, NB2, MDA-MB-231/HER2
研究领域:
癌症研究
·
纳米技术
·
治疗学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
American Journal of Cancer Research
·
2024
·Vol. 14
·期 12
·5752
·
IF 3.6
Xiaobo Cai,Min Cao,Qingliang Yang,Xiazhen Yu,Xin-Hua Feng,Robert Yongxin Zhao
Gastric cancer is a common malignant tumor with high incidence and mortality. The overexpression of Human epidermal growth factor receptor 2 (HER2) is associated with increased metastatic potential and poor clinical outcome in gastric cancer. Despite the proven clinical response rates of approved HER2-targeted therapies, including Trastuzumab combined with chemotherapy, their limited long-term clinical benefits and inevitable disease progression still pose significant challenges to the clinical treatment of gastric cancer. Hence, exploring novel strategies to enhance therapeutic outcomes for HER2-positive patients is extremely crucial and urgent. Here, we reported that DX126-262, a novel HER2-targeted antibody-drug conjugate, generated by conjugating a potent Tubulysin B analogue (Tub-114) to humanized anti-HER2 monoclonal antibody, exhibited a significant synergistic inhibitory effect with both Cisplatin and 5-FU in HER2-positive gastric cancer NCI-N87 cells. Moreover, the triple-drug combination strategy of DX126-262 combined with Cisplatin and 5-FU showed much better in vitro and in vivo therapeutic efficacy than monotherapy or double-drug combination (Cisplatin plus 5-FU) or first-line standard-of-care (SOC, Herceptin plus Cisplatin and 5-FU), and comparable or even superior in vivo efficacy than third-line SOC (DS-8201a) in NCI-N87 cells and xenograft models. Meanwhile, the triple-drug combination therapy did not exhibit superimposed toxicity. Taken together, our findings provide compelling evidence that DX126-262 in combination with Cisplatin and 5-FU exerts synergistic antitumor activity and is a promising strategy to improve the clinical efficacy of HER2-positive advanced or metastatic gastric cancer.
研究领域:
肿瘤学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Ayimukedisi Yalikong,Xu-Quan Li,Ping-Hong Zhou,Zhi-Peng Qi,Bing Li,Shi-Lun Cai,Yun-Shi Zhong
Background Colon cancer (CRC) was a malignant tumor and there were about 25% of patients with tumor metastasis at diagnosis stage. Chemotherapeutic agents for metastatic CRC patients were with great side effects and the clinical treatment results of advanced CRC were still not satisfactory. Human epidermal growth factor receptor 2 (HER2) is overexpressed in some CRC patients and is an effective target for CRC patient treatment. Anti-HER2 therapy had a beneficial role in the treatment of HER2-positive metastatic CRC with fewer side effects. CRC patients with BRAF mutations were resistant to HER2 antibodies treatment. Therefore, there was an urgent need to develop new therapeutic agents.Methods HER2 targeted nanoparticles (TPLNP) drug delivery system loading triptolide (TPL) were prepared and identified. The effects of TPLNP and free TPL on cell viability, targeting and cell cycle progression on HT29 (BRAF mutation) with HER2 overexpression, were evaluated by Cell Counting Kit-8 (CCK8), Fluorescence Activating Cell Sorter (FACS) and immunofluorescence methods, respectively. The anti-tumor efficacies of TPLNP were evaluated in subcutaneous xenograft model of colon cancer and the survival rate, tumor volume, liver and kidney indexes of tumor-bearing mice were measured.Results TPLNP was small in nanosize (73.4±5.2nm) with narrow size distribution (PDI=0.15±0.02) and favorable zeta potential (pH=9.6, zeta potential: −57.3±6.69mV; pH=7.0, zeta potential: −28.7±5.1mV; pH=5.6, zeta potential: −21.1±4.73mV). Comparing with free TPL treatment group, TPLNP developed stranger colon cancer-killing efficiency in a dose- and time-dependent manner detected with CCK8 method; achieved good in vitro colon cancer targeting detected with flow cytometry and immunofluorescence experiments; enhanced more HT29-HER2 apoptosis and induced more cell cycle arrested in G1-S phase detected with FACS in vitro. As for in vivo antitumor response, TPLNP remarkably inhibited the growth of colon cancer in the colon cancer xenograft model, significantly improved the survival rate and did not exhibit significant liver and kidney toxicity in contrast with free TPL in vivo.Conclusion TPLNP was effectively against colon cancer with HER2 overexpression and BRAF mutation in pre-clinical models. In summary, the TPLNP appeared to be a promising treatment option for CRC in clinical application based on improved efficacy and the favorable safety profile.
研究领域:
肿瘤学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANALYTICA CHIMICA ACTA
·
2023
·
IF 6.2
Xiaoxian Liu,Yifan Zhu,Caoxin Li,Yanyun Fang,Jinna Chen,Fei Xu,Yanqing Lu,Perry Ping Shum,Ying Liu,Guanghui Wang
Accurate and ultrasensitive evaluation of human epidermal growth factor receptor 2 (HER2) protein is key to early diagnosis and subtype differentiation of breast cancer. Single-cell analyses to reduce ineffective targeted therapies due to breast cancer heterogeneity and improve patient survival remain challenging. Herein, we reported a novel droplet microfluidic combined with an instant cation exchange signal amplification strategy for quantitative analysis of HER2 protein expression on single cells. In the 160 μm droplets produced by a tapered capillary bundle, abundant Immuno-CdS labeled on HER2-positive cells were replaced by Ag + to obtain Cd 2+ that stimulated Rhod-5N fluorescence. This uniformly distributed and instantaneous fluorescence amplification strategy in droplets improves sensitivity and reduces signal fluctuation. Using HER2 modified PS microsphere to simulate single cells, we obtained a linear fitting of HER2-modified concentration and fluorescence intensity in microdroplets with the limit detection of 11.372 pg mL −1 . Moreover, the relative standard deviation (RSD) was 4.2-fold lower than the traditional immunofluorescence technique (2.89% vs 12.21%). The HER2 protein on SK-BR-3 cells encapsulated in droplets was subsequently quantified, ranging from 9862.954 pg mL −1 and 205.26 pg mL −1 , equivalent to 9.795 × 10 6 and 2.038 × 10 5 protein molecules . This detection system provides a universal platform for single-cell sensitive quantitative analysis and contributes to the evaluation of HER2-positive tumors.
研究领域:
生物技术
·
医学诊断
·
癌症研究
·
微流控
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION
·
2013
·
IF 1.7
Yiyi Wang,Peifeng Liu,Jing Du,Ying Sun,Fenghua Li,Yourong Duan
This study aims to determine the specificity of anti-human epidermal growth factor receptor antibody (anti-HER2) modified monomethoxy polyethylene glycol-chitosan (mPEG-CS) nanoparticles (anti-HER2/mPEG-CS NPs) in delivering small interfering RNA (siRNA) to the human epidermal growth factor receptor 2 (HER2) positive cancer cells. Physicochemical properties of the siRNA-loaded anti-HER2/mPEG-CS NPs (anti-HER2/mPEG-CS-siRNA NPs), including size, surface charge, siRNA encapsulation efficiency, and in vitro release profile of siRNA from NPs, were characterized by particle size and zeta potential analyzer, and ultraviolet–visible spectrophotometer. MTT assay was used to study the in vitro cytotoxicity of the NPs. Fluorescent microscope and flow cytometer analysis results showed that anti-HER2/mPEG-CS-siRNA NPs had much efficient delivery of siRNA than the siRNA alone, Lipofectamine-siRNA complexes and mPEG-CS-siRNA NPs. These results demonstrated that anti-HER2/mPEG-CS-siRNA NPs had great potential applications as a targeted strategy for siRNA delivery.
研究领域:
生物医学工程
·
分子生物学
·
肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
TALANTA
·
2024
·
IF 5.6
Wanmei Guo,Yongsen Yu,Chao Xin,Guangyong Jin
In this study, we present a novel biomarker detection platform employing a modified S-tapered fiber coated with gold nanoparticle/graphene oxide (GNP/GO) for quantifying human epidermal growth factor receptor-2 (HER2) concentrations, using antibodies as sensing elements. The fabrication of this device involves implementing an in-situ layer-by-layer technique coupled with a chemical adsorption step to achieve the self-assembly of GNP, GO, and antibodies on the STF surface. The detection mechanism relies on monitoring the refractive index changes induced by the adsorption of HER2 onto the immobilized antibodies. For comparative analysis, both monoclonal antibody (mAb) and the novel nanobody (Nb) were employed in constructing the STF immunosensor, referred to as the mAb immunosensor and Nb immunosensor, respectively. Spectral analysis results highlight that the Nb immunosensor exhibits twice the sensitivity of the mAb immunosensor. This enhanced sensitivity is attributed to the small size, high antigen affinity, strong specificity, and structural stability of Nb. The Nb immunosensor demonstrated an impressive detection limit of 0.001 nM for HER2, surpassing the detection limit of the mAb immunosensor. These findings underscore the potential of the proposed Nb immunosensor as a promising and sensitive tool for HER2 detection, contributing to the diagnosis and prognosis of breast cancer. Furthermore, the simplicity of production and excellent optical performance position the Nb immunosensor as a prospective real-time biosensor with minimal cytotoxicity.
研究领域:
生物医学工程
·
分子生物学
·
癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomedical Materials
·
2024
·Vol. 19
·期 3
·035034
·
IF 3.9
Qiangqiang Yin,Xiaolong Gao,Hao Zhang,Zhichen Zhang,Xiaoyang Yu,Jialong He,Guangyue Shi,Liguo Hao
This study developed a probe Fe3O4-Cy5.5-trastuzumab with fluorescence and magnetic resonance imaging functions that can target breast cancer with high HER2 expression, aiming to provide a new theoretical method for the diagnosis of early breast cancer. Fe3O4-Cy5.5-trastuzumab nanoparticles were combined with Fe3O4 for T2 imaging and Cy5.5 for near-infrared imaging, and coupled with trastuzumab for HER2 targeting. We characterized the nanoparticles used transmission electron microscopy, hydration particle size, Zeta potential, UV and Fourier transform infrared spectroscopy, and examined its magnetism, fluorescence, and relaxation rate related properties. CCK-8 and blood biochemistry analysis evaluated the biosafety and stability of the nanoparticles, and validated the targeting ability of Fe3O4-Cy5.5 trastuzumab nanoparticles through in vitro and in vivo cell and animal experiments. Characterization results showed the successful synthesis of Fe3O4-Cy5.5-trastuzumab nanoparticles with a diameter of 93.72 ± 6.34 nm. The nanoparticles showed a T2 relaxation rate 42.29 mM−1s−1, magnetic saturation strength of 27.58 emg g−1. Laser confocal and flow cytometry uptake assay showed that the nanoparticles could effectively target HER2 expressed by breast cancer cells. As indicated by in vitro and in vivo studies, Fe3O4-Cy5.5-trastuzumab were specifically taken up and effectively aggregated to tumour regions with prominent NIRF/MR imaging properties. CCK-8, blood biochemical analysis and histological results suggested Fe3O4-Cy5.5-trastuzumab that exhibited low toxicity to major organs and good in vivo biocompatibility. The prepared Fe3O4-Cy5.5-trastuzumab exhibited excellent targeting, NIRF/MR imaging performance. It is expected to serve as a safe and effective diagnostic method that lays a theoretical basis for the effective diagnosis of early breast cancer. This study successfully prepared a kind of nanoparticles with near-infrared fluorescence imaging and T2 imaging properties, which is expected to serve as a new theory and strategy for early detection of breast cancer.
研究领域:
医学影像学
·
肿瘤学
·
纳米医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2024
·
IF 6.1
Miao He,Zhiqiang Hou,Feifan Yin,Wenting Cheng,Yang Xiang,Zhongyun Wang
The detection of a single biomarker is prone to false negative or false positive results. Simultaneous analysis of two biomarkers can greatly improve the accuracy of diagnosis. In this work, we designed a new method for coinstantaneous detection of two breast cancer biomarkers miRNA-21 and HER2 using the properties of duplex-specific nuclease (DSN). Cy5-labeled DNA1 and FAM-labeled DNA2 are used as signal probes to distinguish the two signals. When the sample contains the targets HER2 and miRNA-21, HER2 binds to the HER2 aptamer on the double-stranded DNA2, while miRNA-21 binds to the complementary DNA1. Then, DSN enzyme is added to cut the DNA probes adsorbed on the HER2 aptamer and miRNA-21, releasing the fluorescent groups, which can be readsorbed to the empty sites, thus repeating the cutting of the probes and producing an exponential signal amplification with two distinct fluorescent signals. The detection limits of miRNA-21 and HER2 are 1.12 pM and 0.36 ng mL−1, respectively, with linear ranges of 5 pM to 50 pM and 1 ng mL−1 to 15 ng mL−1. The method was validated in real biological samples, providing a new approach for synchronous analysis of important markers in breast cancer.
研究领域:
生物化学
·
分子生物学
·
医学诊断
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
·
2025
·
IF 4.7
Jingyao Gong,Yunlong Li,Hui Di,Jiamin Li,Junming Dong,Congjie He,Peng Cao,Huiming Cai,Jian He,Yiqing Wang
Combination of PET and optical imaging techniques holds significant potential for complete tumor resection to optimize patient outcomes. In this study, we combined two lapatinib-based molecular probes for detecting HER2-overexoression tumors through PET and near-infrared (NIR) fluorescence imaging. HER2 receptor had been confirmed to be overexpressed in many types of tumors and had become a specific target for molecular imaging. The radiolabeled probe [ 68 Ga] Ga-NOTA-lapatinib demonstrated superior imaging performance in micro-PET scans, achieving clear differentiation of subcutaneous tumors from adjacent tissues. Complementarily, the NIR fluorescent probe LP-S exhibited prolonged tumor retention (>72 h) with distinct signal demarcation between malignant and normal tissues in ex vivo analyses. Fluorescence microscopy further validated specific intra-tumoral accumulation of the probe at cellular resolution. This synchronized dual-probe strategy, leveraging identical targeting moieties, established a robust platform for multimodality cancer imaging that bridges preoperative detection with intraoperative visualization.
研究领域:
医学影像学
·
分子生物学
·
肿瘤学
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Yijia Min,Yu Chen,Lei Wang,Yong Ke,Fan Rong,Qunye He,Pameila Paerhati,Huifang Zong,Jianwei Zhu,Yin Wang,Baohong Zhang
Antibody therapy of anti-HER2 monoclonal antibody (mAb) has been an important strategy in treating HER2-positive cancers. However, the efficacy is restricted by many factors, including the level of HER2 expressed by tumor cells and antibody resistance. To overcome these and boost the efficacy, a novel nanoparticle (NP) was constructed in this study for combined antibody therapy of antibody and photothermal therapy (PTT). This novel NP was assembled from 1-pyrenecarboxylic acid (PCA) functionalized anti-HER2 mAb and indocyanine green (ICG), a photothermal transduction agents (PTA), by non-covalent interactions, which was named as Anti-HER2 mAb-pyrene-indocyanine green (H-P-I). Notably, the constructed H-P-I NP not only maintained the affinity and cytotoxicity of anti-HER2 mAb, but also exhibited high photothermal conversion efficiency mediated by ICG. Both in vitro and in vivo assessments confirmed that compared with monotherapy of antibody or ICG, H-P-I demonstrated preferable efficacy in treating HER2-positive cancers. Further biochemistry analysis and pathological analysis ensured the biosafety of H-P-I administration. Taked together, this study proposes a feasible method for constructing tumor-targeted nano PTA based on anti-HER2 mAb through supramolecular self-assembly strategy, achieving synergistic antibody photothermal anticancer treatment, which has the potential to be a promising candidate for combination therapy of HER2-positive cancers.
研究领域:
癌症治疗
·
纳米技术
·
生物医学工程
·
药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Oncology Letters
·
2018
·Vol. 15
·期 5
·8079-8087
·
IF 1.664
Daren Liu,Xiaowen Li,Changlei Chen,Chao Li,Chuanbiao Zhou,Weidong Zhang,Jiangang Zhao,Jie Fan,Kai Cheng,Li Chen
Gastric cancer is the fourth most common malignancy globally. In order to decrease the dosage and side effects of conventional chemotherapy, and achieve improved benefits from molecular targeted therapy, novel drug delivery systems were developed in the present study. Oxaliplatin‑Au‑Fe3O4‑Herceptin® acts as a dual‑functional nanoparticles (NPs) conjugate and possesses the capability of human epithelial growth factor receptor 2 (HER2) targeting and oxaliplatin delivery. The 8‑20 nm Au‑Fe3O4 were synthesized by decomposing iron pentacarbonyl on the surfaces of Au NPs in the presence of oleic acid and oleylamine. Following being coated with polyethylene glycol, the NPs possessed a ζ‑potential of 13.8±1.6 mV and were demonstrated to exhibit no cytotoxicity when Fe concentration is <100 µg/ml via an MTS assay. Mass spectrometry analysis detected a peak at m/z 148,000, and Nuclear Magnetic Resonance indicated peaks at δ 3.51 (8.00H, s, 3‑H), 2.97‑3.02 (3.80H, t, 2‑H) and 2.72‑2.76 (3.72H, t, 1‑H) following successful loading with Herceptin and oxaliplatin probes. A drug release assay via dialysis cassettes demonstrated that 25% of the oxaliplatin was released at pH 8.0, however >58% was released at pH 6.0 following 4 h incubation, indicating its pH‑dependent release characteristic. The active targeting feature of oxaliplatin‑Au‑Fe3O4‑Herceptin was verified in a subcutaneous xenograft mouse model containing SGC‑7901 cells via detecting aggregated low intensity in T2‑weighted magnetic resonance imaging, which was further confirmed by immunohistochemistry. Therefore, oxaliplatin‑Au‑Fe3O4‑Herceptin is a promising multifunctional platform for simultaneous magnetic traceable and HER2 targeted chemotherapy for gastric cancer.
研究领域:
肿瘤学
·
纳米医学
·
药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR PHARMACEUTICS
·
2017
·
IF 4.44
Di Gao,Jinbiao Gao,Ming Xu,Zhong Cao,Luyao Zhou,Yingqin Li,Xiaoyan Xie,Qing Jiang,Wei Wang,Jie Liu
For successful gene therapy, it is imperative to accumulate therapeutic gene in tumor tissues followed by efficiently delivering gene into targeted cells. Ultrasound irradiation, as a noninvasive and cost-effective external stimulus, has been proved to be one of the most potential external-stimulating gene delivery strategies recently in further improving gene transfection. In this study, we developed tumor-targeting ultrasound-triggered phase-transition nanodroplets AHNP-PFP-TNDs comprising a perfluorinated poly(amino acid) C11F17–PAsp (DET) as a core for simultaneously loading perfluoropentane (PFP) and nucleic acids, and a polyanionic polymer PGA-g-PEG-AHNP as the shell for not only modifying the surface of nanodroplets but also introducing an anti-Her2/neu peptide (AHNP) aiming to targeted treatment of Her2-overexpressing breast cancer. The results showed the average diameter of AHNP-PFP-TNDs was below 400 nm, nearly spherical in shape. The modification of PGA-g-PEG-AHNP not only increased the serum stability of the nanodroplets but also improved the affinity between nanodroplets and Her2-overexpressing breast cells. Both intratumor and intravenous injection of AHNP-PFP-TNDs into nude mice bearing HGC-27 xenografts showed that the gene transfection efficiency and the ultrasound contrast effect were significantly enhanced after exposed to the ultrasound irradiation with optimized ultrasound parameters. Therefore, this targeting nanodroplets system could be served as a potential theranostic vector for tumor targeting ultrasound diagnosis and gene therapy.
研究领域:
医学影像学
·
肿瘤学
·
基因治疗
✓ 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）