Paclitaxel-functionalized gold nanoparticles.
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.
Gibson
Jacob D
JD
Department of Chemistry, Rice University, Houston, Texas 77005, USA.
Khanal
Bishnu P
BP
Zubarev
Eugene R
ER
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry*; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D006046:Gold / Q000737:chemistry*; D053768:Metal Nanoparticles / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D017239:Paclitaxel / Q000008:administration & dosage / Q000737:chemistry*
D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D006046:Gold; D017239:Paclitaxel