Hyaluronic Acid-Modified and Doxorubicin-Loaded Gold Nanoparticles and Evaluation of Their Bioactivity

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.

Hyaluronate-Thiol Passivation Enhances Gold Nanoparticle Peritumoral Distribution When Administered Intratumorally in Lung Cancer

“…Many research works present different synthesis processes of HA-GNP complexes [ 49 ], as well as their in vitro testing as drug carriers for photothermal cytotoxic drug release in cancer cells [ 50 ]. We identified certain studies involving pre-clinical cancer models; however, the HA coated GNPs are only administered systemically, and biodistribution is not evaluated [ 51 , 52 , 53 , 54 ]. Only a few studies have assessed HA-GNP distribution in various pre-clinical models, such as the porcine eye, as HA is a widely used excipient in ocular drug delivery, and rodent skin, as HA has the ability to stimulate fibrin development in the wound healing process.…”

Enhanced photothermal heating and combination therapy of gold nanoparticles on a breast cell model

“…In addition, the greater electrostatic attraction of active groups in Dox with AuNPs than citrate groups might be responsible for the additional band at higher wavelengths. It has been shown theoretically and experimentally that aggregation of AuNPs leads to another plasmon absorption at longer wavelengths when the individual nanoparticles are electronically coupled to each other [ 22 ]. TEM images of Dox@AuNPs nanocomposite Fig.…”

“…Cancer remains one of the major causes of death despite recent advancements in cancer treatment [ 1 ]. In 2020, 2.7 million people in the European Union were diagnosed with the disease, and another 1.3 million people lost their lives to it [ 2 ]. The world invests tens of billions of dollars and huge human capital every year in the development of new anti-tumor drugs.…”

Evaluation of the Biological Activity of Folic Acid-Modified Paclitaxel-Loaded Gold Nanoparticles

“…[8][9][10] Importantly, AuNPs can be effectively modified for specific targeting to reduce premature drug release. [11][12][13][14][15] Paclitaxel (PTX), approved by the US FDA in 1992, is a key drug to treat advanced cancer. Particularly, it has been effective against breast and ovarian cancer while also showing good apoptotic effects against other tumor cells.…”