Delivery Capacity and Anticancer Ability of the Berberine-Loaded Gold Nanoparticles to Promote the Apoptosis Effect in Breast Cancer

Abstract

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.

Therapeutic Applications of Mesenchymal Stem Cell Loaded with Gold Nanoparticles for Regenerative Medicine

“…Additionally, AuNPs can be functionalized with targeting molecules, such as antibodies or aptamers, allowing for targeted drug delivery to specific cell types or tissues [ 61 ]. Additionally, our studies have verified that AuNPs modified with collagen are a biocompatible nanodrug delivery system that can carry natural compounds and has demonstrated good anti-cancer capacities [ 18 , 62 ]. However, since the higher concentration of AuNP may lead to cytotoxicity, the mission to select appropriate concentration of nanoparticles to develop a nanodrug delivery system becomes important for regenerative therapies [ 40 ].…”

Berberine as a potential agent for breast cancer therapy

“…Qin et al found that a conjugator via linker BBR to platinum (II) complex significantly improved the in vitro and in vivo anti-BC activity (134). In addition, drug delivery using nanocarriers is widely used to improve cell penetration, biocompatibility, and in vivo efficacy, and this method is also an applicant for improving bioavailability and the efficacy of BBR against BC (135)(136)(137). Moreover, chemical modification is also a potent strategy to improve cell penetration, and water soluble anti-tumor activity of BBR and several BBR derivatives have been designed and exhibited better anti-BC efficacy than their lead compound BBR (132,(138)(139)(140)(141).…”

(Nano)platforms in breast cancer therapy: Drug/gene delivery, advanced nanocarriers and immunotherapy

“…Apoptosis was responsible for the decreased progression of breast tumor by berberine-loaded gold nanoparticles, and upregulation of Bax and p21 were observed. 31 The resveratrol-loaded gold nanostructures had 30.75 nm size and −32.8 mV zeta potential. The resveratrol-loaded gold nanoparticles suppressed the growth and metastasis of breast cancer cells via through suppressing MMP-9 and COX-2.…”

“…Berberine was loaded onto gold nanoparticles and they were internalized through clathrin‐mediated endocytosis and autophagy, and they significantly decreased the viability. Apoptosis was responsible for the decreased progression of breast tumor by berberine‐loaded gold nanoparticles, and upregulation of Bax and p21 were observed 31 . The resveratrol‐loaded gold nanostructures had 30.75 nm size and −32.8 mV zeta potential.…”