Abstract
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.
Highlights
The latest statistical data has shown that female breast cancer surpassed lung cancer for the first time, and became the most common cancer in the world (Sung et al, 2021)
In order to verify whether nanobody 2 (NB2) can recognize the HER2 extracellular domain (HER2 ECD) protein, firstly, the HER2 ECD protein was analyzed to express successfully in BL21-DE3 (Figure 2E, Supplementary Figure S1)
NB2 was used as the primary antibody to identify HER2 ECD protein, and the GST tag antibody was used as the secondary antibody to recognize NB2
Summary
The latest statistical data has shown that female breast cancer surpassed lung cancer for the first time, and became the most common cancer in the world (Sung et al, 2021). Human epidermal growth factor receptor-2 (HER2) is an important prognostic factor of breast cancer. About 20–30% of breast cancer patients with overexpression of HER2 generate highly invasive, short disease-free survival and poor prognosis (Baselga, 2006). HER2 was frequently used as the target in breast cancer targeted therapy (Oh and Bang, 2020). The anti-HER2 targeted drugs have greatly improved the therapeutic effect of HER2-positive breast cancer patients (Loibl and Gianni, 2017). Pertuzumab and Trastuzumab combined with Docetaxel are the main first-line standard treatment for Her2-positive breast cancer
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