Micellear Gold Nanoparticles as Delivery Vehicles for Dual Tyrosine Kinase Inhibitor ZD6474 for Metastatic Breast Cancer Treatment

The therapeutic index of poorly water-soluble drugs is often hampered due to poor pharmacokinetics, reduced blood retention, and lack of effective drug concentrations in the tumor region. In order to overcome these issues, drugs are often delivered by use of delivery vehicles to provide an enhanced therapeutic index. Gold nanoparticles synthesized in micellar networks of amphiphilic block copolymer (AuNM) provide an efficient nanocarrier for tissue- and site-specific drug delivery owing to their low cytotoxicity and immunogenicity. AuNM is formed by exploiting the properties of both inorganic Au material and an amphiphilic polymer of poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) (PEG–PPG–PEG). We further functionalized AuNM with the FDA-approved dual tyrosine kinase inhibitor ZD6474 and studied the physicochemical properties of the conjugate ZD6474–AuNM. Both AuNM and ZD6474–AuNM, with a diameter of ∼70 nm, were very stable at physiological pH. Conversely, at an acidic pH ...