Abstract
Functionalized gold nanoparticles (AuNPs) have been successfully used in many fields as a result of having low cytotoxicity, good biocompatibility, excellent optical properties, and their ability to target cancer cells. Here, we synthesized AuNP carriers that were modified by hyaluronic acid (HA), polyethylene glycol (PEG), and adipic dihydrazide (ADH). The antitumor drug doxorubicin (Dox) was loaded into AuNP carriers and attached chemically. The Au nanocomposite AuNPs@MPA-PEG-HA-ADH-Dox was able to disperse uniformly in aqueous solution, with a diameter of 15 nm. The results of a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay indicated that AuNP carriers displayed very little toxicity toward cells in high doses, although the antitumor properties of Au nanocomposites were significantly enhanced. Cellular uptake experiments demonstrated that AuNPs modified with hyaluronic acid were more readily ingested by HepG2 and HCT-116 cells, as they have a large number of CD44 receptors. A series of experiments measuring apoptosis such as Rh123 and annexin V-FITC staining, and analysis of mitochondrial membrane potential (MMP) analysis, indicated that apoptosis played a role in the inhibition of cell proliferation by AuNPs@MPA-PEG-HA-ADH-Dox. Excessive production of reactive oxygen species (ROS) was the principal mechanism by which the Au nanocomposites inhibited cell proliferation, leading to apoptosis. Thus, the Au nanocomposites, which allowed cell imaging in real-time and induced apoptosis in specific cell types, represent theragnostic agents with potential for future clinical applications in bowel cancer.
Highlights
Gold nanoparticles (AuNPs) are used in cancer diagnosis and biological imaging because of their excellent optical properties, low cytotoxicity, and good biocompatibility [1–5]
The ligand Polyethylene glycol (PEG)-Hyaluronic acid (HA)-adipic dihydrazide (ADH) was synthesized through chemical synthesis (Scheme 2), while the 1 Hydrogen-Nuclear Magnetic Resonance (1 H NMR) spectrum (Figure S2) and Fourier transform infrared (FTIR) spectrum (Figure S3) were used to evaluate the reaction
Au particles with a diameter of 15 nm were obtained by boiling, after which PEG-HA-ADH ligands were grafted onto the surface with chemical bonds, obtaining the modified form of AuNPs, Au@mercaptopropionic acid (MPA)-PEG-HA-ADH
Summary
Gold nanoparticles (AuNPs) are used in cancer diagnosis and biological imaging because of their excellent optical properties, low cytotoxicity, and good biocompatibility [1–5]. AuNPs have received considerable attention by many researchers [6–10], as it has been frequently reported that they can induce programmed cell death (i.e., apoptosis) [11,12]. As drug carriers, AuNPs can transport imaging and therapeutic agents, providing the possibility of diagnosis, treatment, and monitoring therapeutic progress, while AuNPs themselves do not participate in diagnosis or therapy [13–17]. AuNPs are rarely reported as agents that can inhibit cell proliferation and achieve both fluorescence-enhanced cell imaging and specific cell targeting. Improvements in functionalized AuNPs represent an important trend in cancer treatment research [18]. We aimed to design a sensitive and specific agent using AuNPs that inhibits cell proliferation and allows fluorescence enhanced cell imaging
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