Isolipoic acid-linked gold nanoparticles bearing the thomsen friedenreich tumor-associated carbohydrate antigen: Stability and in vitro studies

Abstract

We have previously prepared gold nanoparticles (AuNPs) bearing the Thomsen-Friedenreich antigen disaccharide (TFag), a pan-carcinoma, Tumor-Associated Carbohydrate Antigen (TACA), as tools for various assays and biological applications. Conjugation to AuNPs typically involves the use of thiols due to the affinity of sulfur for the gold surface of the nanoparticle. While a use of a single thiol-containing ligand bound to the gold surface is standard practice, several studies have shown that ligands bearing multiple thiols can enhance the strength of the conjugation in a nearly linear fashion. (R)-(+)-α-Lipoic acid (LA), a naturally occurring disulfide-containing organic acid that is used as a cofactor in many enzymatic reactions, has been used as a linker to conjugate various molecules to AuNPs through its branched di-thiol system to enhance nanoparticle stability. We sought to use a similar system to increase nanoparticle stability that was devoid of the chiral center in (R)-(+)-α-lipoic acid. Isolipoic acid, an isomer of LA, where the exocyclic pentanoic acid chain is shifted by one carbon on the dithiolane ring to produce an achiral acid, was thought to act similarly as LA without the risk of any contaminating (L)-(−) isomer. We synthesized AuNPs with ligands of both serine and threonine glycoamino acids bearing the TFag linked to isolipoic acid and examined their stability under various conditions. In addition, these particles were shown to bind to Galectin-3 and inhibit the interaction of Galectin-3 with a protein displaying copies of the TFag. These agents should prove useful in the design of potential antimetastatic therapeutics that would benefit from achiral linkers that are geometrically linear and achiral.

Tackling breast cancer with gold nanoparticles: twinning synthesis and particle engineering with efficacy

“…194 AuNPs with glycoamino acids ligands bearing the Thomsen-Friedenreich antigen linked to isolipoic acid had a profound inuence on stability enhancement of AuNPs without hindering their biological action. 195 Phthalocyanine-AuNPs engineered with lactose were reported to produce singlet oxygen and effect cell death upon irradiation as well as be associated with the galectin-1 receptor on the surface of BC cells. 196 Carbohydrates as glycolipids or glycoproteins serve as important signalling moieties of our bodies.…”

Nanotechnological Approaches to Enhance the Potential of α-Lipoic Acid for Application in the Clinic

“…DTT was also used to induce the polymerization of α-lipoic acid contained in a dimeric surfactant-like amphiphilic molecule: this molecule can form nanoaggregates, due to the hydrophobic head of α-lipoic acid and the hydrophilic tail of gemini surfactant. Nanoaggregates were then stabilised thanks to α-lipoic acid polymerization and loaded with doxorubicin: the nanonetwork was selectively cytotoxic against cancer cells with respect to normal cells [ 195 ].…”