Abstract
Simple SummaryIn this research, we aimed to evaluate the biological effects of physically gold nanoparticle-collagen nanocarrier incorporated with alkaloid berberine (Au-Col-BB) on non-transformed bovine aortic endothelial cells (BAEC) and Her-2 breast cancer cell lines through in vitro and in vivo assessments. Au-Col-BB showed better cytotoxicity, as well as significantly induced cell apoptosis in Her-2 cancer cells compared with normal cells (non-transformed BAEC). Further, Au-Col-BB also demonstrated better anti-cancer capacity for inhibiting cell growth in Her-2 tumor-bearing mice. In brief, we confirmed that the Au-Col-BB nanocarrier could be a potential nanodrug for increasing the efficiency of specific therapeutic effects in breast cancer disease.Gold nanoparticles (AuNPs) were fabricated with biocompatible collagen (Col) and then conjugated with berberine (BB), denoted as Au-Col-BB, to investigate the endocytic mechanisms in Her-2 breast cancer cell line and in bovine aortic endothelial cells (BAEC). Owing to the superior biocompatibility, tunable physicochemical properties, and potential functionalization with biomolecules, AuNPs have been well studied as carriers of biomolecules for diseases and cancer therapeutics. Composites of AuNPs with biopolymer, such as fibronectin or Col, have been revealed to increase cell proliferation, migration, and differentiation. BB is a natural compound with impressive health benefits, such as lowering blood sugar and reducing weight. In addition, BB can inhibit cell proliferation by modulating cell cycle progress and autophagy, and induce cell apoptosis in vivo and in vitro. In the current research, BB was conjugated on the Col-AuNP composite (“Au-Col”). The UV-Visible spectroscopy and infrared spectroscopy confirmed the conjugation of BB on Au-Col. The particle size of the Au-Col-BB conjugate was about 227 nm, determined by dynamic light scattering. Furthermore, Au-Col-BB was less cytotoxic to BAEC vs. Her-2 cell line in terms of MTT assay and cell cycle behavior. Au-Col-BB, compared to Au-Col, showed greater cell uptake capacity and potential cellular transportation by BAEC and Her-2 using the fluorescence-conjugated Au-Col-BB. In addition, the clathrin-mediated endocytosis and cell autophagy seemed to be the favorite endocytic mechanism for the internalization of Au-Col-BB by BAEC and Her-2. Au-Col-BB significantly inhibited cell migration in Her-2, but not in BAEC. Moreover, apoptotic cascade proteins, such as Bax and p21, were expressed in Her-2 after the treatment of Au-Col-BB. The tumor suppression was examined in a model of xenograft mice treated with Au-Col-BB nanovehicles. Results demonstrated that the tumor weight was remarkably reduced by the treatment of Au-Col-BB. Altogether, the promising findings of Au-Col-BB nanocarrier on Her-2 breast cancer cell line suggest that Au-Col-BB may be a good candidate of anticancer drug for the treatment of human breast cancer.
Highlights
Cancer diseases are leading reasons of death around the world
The brief concept elucidates the procedures for manufacturing gold nanoparticles conjugated with collagen and berberine (Figure 1A)
The surface potential of different nanoparticles was evaluated by dynamic light scattering (DLS) analyzer
Summary
Cancer diseases are leading reasons of death around the world. Cancer cells trigger apoptosis resistance, metastasis, inflammation, and the breakdown of intercellular communication that cause poor immune response. The treatments of cancer include several clinical therapies, such as surgery, radiation, and chemotherapy. Chemotherapy is an effective procedure to decrease the volume of primary tumor before surgery, a long-term chemotherapy treatment can cause various side effects, such as nausea, vomiting, fatigue, hair loss, leukopenia, mucositis, neurosensory disorders, and taste alterations in cancer patients, and induce multidrug resistance [1,2,3,4]. New drug development for cancer diseases requires plenty of time and costs expensive [5]. A literature figured out “Drug repurposing” to be a clinical strategy through the use of approved drugs for breast cancer therapeutics [5], such as the combination of insulin like growth factor 1 receptor (IGF1R) inhibitors with approved drug Rapamycin [6] demonstrates the inhibition of breast cancer cells proliferation [7]
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