We report here the synthesis of multifunctional dendrimer-entrapped gold nanoparticles (Au DENPs) modified with alpha-tocopheryl succinate (α-TOS) and arginine-glycine-aspartic acid (RGD) peptide for targeted chemotherapy and computed tomography (CT) imaging of cancer cells. In this work, generation 5 poly(amidoamine) dendrimers pre-conjugated with fluorescein isothiocyanate (FI), RGD peptide via a polyethylene glycol (PEG) spacer, and PEG-linked α-TOS were used as templates to synthesize AuNPs. Followed by acetylation of the remaining dendrimer terminal amines, multifunctional Au DENPs with an Au core size of 4.0nm were generated. The formed multifunctional Au DENPs were characterized via different techniques. We show that the multifunctional Au DENPs are stable at different pH (5-8) and temperature (4-50°C) conditions and display enhanced efficacy in the generation of reactive oxygen species, which is associated with their increased ability to induce apoptosis. Thanks to the role played by RGD-mediated targeting, the multifunctional Au DENPs are able to target cancer cells overexpressing αvβ3 integrin and specifically inhibit the growth of the cancer cells. Likewise, the existence of AuNPs enabled the multifunctional Au DENPs to have a better X-ray attenuation property than clinically used iodinated CT contrast agents (e.g., Omnipaque) and the use of them as a nanoprobe for targeted CT imaging of cancer cells in vitro. The formed multifunctional Au DENPs may hold great promise to be used as a theranostic platform for cancer theranostics.
Keywords: Alpha-tocopheryl succinate; Dendrimers; Gold nanoparticles; RGD peptide; Theranostics.
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