Synthesis and Evaluation of Glycopolymeric Decorated Gold Nanoparticles Functionalized with Gold-Triphenyl Phosphine as Anti-Cancer Agents

Abstract

In this study, statistical glyco-dithiocarbamate (DTC) copolymers were synthesized by reversible addition-fragmentation chain transfer polymerization (RAFT) and subsequently used to prepare glyconanoparticles and conjugated glyconanoparticles with the anticancer drug, gold(I) triphenylphosphine. These glyconanoparticles and the corresponding conjugates were then tested for their in vitro cytotoxicity in both normal and cancer cell lines using Neutral Red assay. The glyconanoparticles and their Au(I)PPh3 conjugates were all active against MCF7 and HepG2 cells, but galactose-functionalized glyconanoparticles {P(GMA-EDAdtc(AuPPh3)-st-LAEMA)AuNP} were found to be the most cytotoxic to HepG2 cells (IC50 ∼ 4.13 ± 0.73 μg/mL). The p(GMA-EDAdtc(AuPPh3)-st-LAEMA)AuNP was found to be a 4-fold more potent antitumor agent in HepG2 cells, and the overexpressed asialoglycoprotein (ASGPR) receptors revealed to play an important role in the cytotoxicity, presumably by the enhanced uptake. In addition, the glyconanoparticles Au(I) conjugates are found to be significantly more toxic as compared to the standard chemotherapeutic reagents such as cisplatin and cytarabine.

Glyco-gold nanoparticles: synthesis and applications

“…Recently, it has been reported the interesting synthesis of AuNPs coated with glyco-polymers and functionalized with gold(I) triphenylphosphine (Fig. 7) [88]. This work showed the potentiality of these structures as novel cancer therapeutic drugs.…”

Carbohydrate-Based Materials for Targeted Delivery of Drugs and Genes to the Liver

“…Reproduced with permission from [55]. Reproduced with permission from [59]. Others have shown that lactose modified super paramagnetic iron oxide nanoparticles and gold nanoparticles significantly accumulate in mice liver and were used as source of computed tomography [57,58].…”

“…The amine content of cationic glycopolymers was modified with dithiocarbamate motif, in a postpolymerization modification approach. Dithiocarbamate and gold triphosphine Au(PPh 3 )Cl-functionalized gold nanoparticles were then prepared by UV reduction of gold salt, as shown in Figure 19 [59].…”

“…Galactose-targeted glyconanoparticles showed ASGPR-dependent uptake in HepG2, as determined by AF competition assay. The substantially high toxicities of nanoparticles in HepG2 cells were attributed toward their selective uptake in hepatocytes [59].…”

Stimuli-responsive multifunctional glyconanoparticle platforms for targeted drug delivery and cancer cell imaging

“…49–54 Enhanced fluorescence, which stems from the GSH-mediated cleavage of NA-S-BA, was observed in ASGPR-expressing HepG2 cells as compared to ASGPR-deficient cancer cells (HeLa cells) and ASGPR-deficient non-tumorigenic cells (NIH3T3 cells). 55,56 Accordingly, nanoparticles conjugated with CPT-S-BA exhibit distinct selectivity for cancer cells over normal cells, without compromising the chemotherapeutic efficacy of the native CPT. A noteworthy advantage is that by simply changing the carbohydrate moiety on the GNP, this system possesses the potential to target a variety of cancer cells based on the lectins expressed on the cell surface and the corresponding conjugated carbohydrates.…”