International Journal of Nanomedicine (Oct 2021)
Evaluation of the Biological Activity of Folic Acid-Modified Paclitaxel-Loaded Gold Nanoparticles
Abstract
Bin Ren,1,2,* Zhong-Chao Cai,1,* Xue-Jie Zhao,1 Lin-Song Li,1 Mei-Xia Zhao1 1Key Laboratory of Natural Medicine and Immuno-Engineering of Henan Province, Henan University, Jinming Campus, Kaifeng, Henan, 475004, People’s Republic of China; 2School of Mathematics and Statistics, Henan University, Jinming Campus, Kaifeng, 475004, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mei-Xia ZhaoKey Laboratory of Natural Medicine and Immune Engineering of Henan Province, Henan University, Jinming Campus, Kaifeng, Henan, 475004, People’s Republic of ChinaEmail [email protected]: Gold nanoparticles (AuNPs) with good physical and biological properties are often used in medicine, diagnostics, food, and similar industries. This paper explored an AuNPs drug delivery system that had good target selectivity for folate-receptor overexpressing cells to induce apoptosis.Methods: A novel drug delivery system, Au@MPA-PEG-FA-PTX, was developed carrying paclitaxel (PTX) on folic acid (FA) and polyethylene glycol (PEG)-modified AuNPs. The nanomaterial was characterized by transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), and ultraviolet-visible spectroscopy (UV-Vis). Also, the biological activity of the AuNPs drug delivery system was examined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in HL-7702, Hela, SMMC-7721, and HCT-116 cells. Furthermore, apoptotic activity using annexin V-FITC, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) levels was estimated by flow cytometry and fluorescence microscopy.Results: Au@MPA-PEG-FA-PTX exhibited a distinct core-shell structure with a controllable size of 28± 1 nm. Also, the AuNPs maintained good dispersion and spherical shape uniformity before and after modification. The MTT assay revealed good antitumor activity of the Au@MPA-PEG-FA-PTX against the Hela, SMMC-7721, and HCT-116 cells, while Au@MPA-PEG-FA-PTX produced better pharmacological effects than PTX in isolation. Further mechanistic investigation revealed that effective internalization of AuNPs by folate-receptor overexpressing cancer cells induced cell apoptosis through excessive production of intracellular ROS.Conclusion: The AuNPs drug delivery system showed good target selectivity for folate-receptor overexpressing cancer cells to induce target cell-specific apoptosis. These AuNPs may have great potential as theranostic agents such as in cancer.Keywords: gold nanoparticles, folic acid, paclitaxel, drug delivery system, apoptosis
