Paclitaxel-Functionalized Gold Nanoparticles

Abstract

Here we describe the first example of 2 nm gold nanoparticles (Au NPs) covalently functionalized with a chemotherapeutic drug, paclitaxel. The synthetic strategy involves the attachment of a flexible hexaethylene glycol linker at the C-7 position of paclitaxel followed by coupling of the resulting linear analogue to phenol-terminated gold nanocrystals. The reaction proceeds under mild esterification conditions and yields the product with a high molecular weight, while exhibiting an extremely low polydispersity index (1.02, relative to linear polystyrene standards). TGA analysis of the hybrid nanoparticles reveals the content of the covalently attached organic shell as nearly 67% by weight, which corresponds to approximately 70 molecules of paclitaxel per 1 nanoparticle. The presence of a paclitaxel shell with a high grafting density renders the product soluble in organic solvents and allows for detailed (1)H NMR analysis and, therefore, definitive confirmation of its chemical structure. High-resolution TEM was employed for direct visualization of the inorganic core of hybrid nanoparticles, which were found to retain their average size, shape, and high crystallinity after multiple synthetic steps and purifications. The interparticle distance substantially increases after the attachment of paclitaxel as revealed by low-magnification TEM, suggesting the presence of a larger organic shell. The method described here demonstrates that organic molecules with exceedingly complex structures can be covalently attached to gold nanocrystals in a controlled manner and fully characterized by traditional analytical techniques. In addition, this approach gives a rare opportunity to prepare hybrid particles with a well-defined amount of drug and offers a new alternative for the design of nanosized drug-delivery systems.

In vitro and in vivo toxicity assessment of nanoparticles

“…Nanoparticles are used in additives for paints, ceramics, foods, paper, packaging, drug delivery, biosensor and cancer therapy [4]. They are also used as tumour detector [5], paclitaxel [6] and radiotherapy dose enhancer [7,8]. They are in demand due to their small size and greater surface area to volume ratio [9].…”

Bactericidal Activity of Copper Oxide Nanocomposite/Bioglass for in Vitro Clindamycin Release in Implant Infections Due to Staphylococcus aureus

“…Some studies have emphasized the toxicity of nanoparticles in in vivo conditions, considering the molecular effects of some nanoparticles with different concentrations and shapes in the tissues of laboratory animals prior to use on humans (47). Significant scientific achievements involving nanotechnology have also been found for gold nanoparticles (48).…”

Multifunctional Gold Nanocarriers for Cancer Theranostics: From Bench to Bedside and Back Again?

“…AuNPs are also being investigated as vehicles for drug delivery such as paclitaxel (Gibson et al, 2007). Gibson et al describe the first example of 2 nm AuNPs covalently functionalized with the chemotherapeutic drug paclitaxel.…”

“…The administrations of hydrophobic drugs require molecular encapsulation and it is found that nanosized particles are particularly efficient in evading the reticuloendothelial system. This approach gives a rare opportunity to prepare hybrid particles with a well-defined amount of drug and offers a new alternative for the design of nanosized drug-delivery systems (Kim et al, 2009a;Hwu et al, 2009;Gibson et al, 2007) (see Figure 4) Nanotechnology has provided for novel and powerful systems that may be used treatment of human diseases. However the majority of products, reagents and drugs being used for the development of these nanoscale systems have to be approved by the main supervising agencies, such as the FDA and EMA (Baptista, 2009).…”