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  • br Experimental section The parts of chemicals and regents p

    2022-04-11


    Experimental section The parts of chemicals and regents, preparation of solutions, pre-treatment of the bare Au electrode, cell culture, cytotoxicity in vitro, cell imaging, characterizations, and electrochemical measurements are supplied in the S1 (See the Supplementary Information). The preparation procedures of Hf-MOF, Zr-MOF, ZrHf-MOF, and CDs are supplied in S1.2 and 1.3.
    Results and discussion
    Conclusion In summary, a novel nanocomposite CDs@ZrHf-MOF was designed and synthesized by embedding the amino-functionalized CDs into bimetallic ZrHf-MOF, leading to good electrochemical activity, excellent biocompatibility and defective nanostructure. The strong binding of aptamer strands endows the CDs@ZrHf-MOF-based aptasensor with high detecting sensitivity toward HER2 and MCF-7 cells. Notably, the synergistic effect of CDs, Zr-MOF, and Hf-MOF can not only facilitate the enhancement of electrochemical activity but also improve the RVX-208 of the formed G-quadruplex between the aptamer strands and HER2. As such, the CDs@ZrHf-MOF-based aptasensor shows an extremely LOD of 19 fg mL−1 and 23 cell mL−1 toward HER2 and MCF-7 cells, respectively, along with good selectivity, stability, reproducibility, and acceptable applicability. Though the validation of this aptasensor can be revealed using human serum samples, its application needs to be further evaluated in future using the real time clinical specimens.
    Introduction Breast cancer is the most common cancer in women worldwide, with almost 2 million new breast cancer diagnoses each year. In the United States, there were an estimated 268,670 cases of invasive cancer in 2018, 6% of which presented as stage IV disease. Survival for patients with metastatic breast cancer has steadily improved over the last several decades.3, 4 Ruiterkamp et al noted median overall survival (OS) for de novo stage IV breast cancer increased from 1.42 years (1995-1999) to 1.95 years (2005-2008). Patient outcomes and length of survival are dependent on many factors, including receptor status and site of metastasis.5, 6, 7, 8, 9 It is often the heterogenous nature of breast cancer that causes tailoring of treatment for these patients to be a challenge for clinicians.10, 11 Targeted therapy for breast cancer, especially metastatic disease, has been utilized for over 100 years. Endocrine therapy for metastatic breast cancer is one of the oldest effective therapies, with Beatson noting the benefits of oophorectomy in the 1800s. Work by various researchers on tamoxifen and the estrogen receptor (ER) in the 1960s led to the institution of targeted therapy in the 1970s. The Early Breast Cancer Trialists’ Collaborative Group results solidified support for targeted therapy for hormone receptor positive breast cancer. Further targeted therapy was developed after the discovery of human epidermal growth factor receptor 2 (HER2) as a potential target in breast cancer. Early studies by Slamon et al examined the effect of trastuzumab added to chemotherapy in the metastatic setting and noted a longer time to disease progression and an increase in median OS in patients with HER2+ breast cancer by 5 months. In the Cleopatra trial, the addition of another HER2-targeted agent, pertuzumab, to trastuzumab and docetaxel improved median OS to 56.5 months, versus 40.8 months with trastuzumab and docetaxel alone. More recent studies examined T-DM1 (trastuzumab emtansine), with improvements in median OS of 25% to 32% in previously treated patients with metastatic HER2+ breast cancer.
    Patients and Methods
    Results
    Discussion The outcomes of breast cancer patients with metastatic disease is known to vary on the basis of the receptor status of the tumor. The analysis of HER2+ metastatic breast cancer has often been a combined analysis, with disregard for the ER status of the disease.18, 19 This detailed analysis of data from NCDB and SEER clearly defines the role of ER status in HER2+ breast cancer in terms of site of distant metastasis, OS, and BCSS.