Y-Shaped Ligand-Driven Gold Nanoparticles for Highly Efficient Tumoral Uptake and Photothermal Ablation

We report functional gold nanoparticles (AuNP) with antibody-like ligands. These particles consist of Y-shaped ligands and AuNP. Transferrin (Tf) and Tat peptide were linked to each head of a Y-shaped poly(ethylene glycol) (PEG)-containing dopamine at one tail site. Also, Y-shaped ligands (with Tf and Tat peptide) were anchored to the surface of the AuNP as the result of noncovalent conjugation of dopamine and the AuNP. Interestingly, the partial shielding of Tat peptides by large Tf molecules rather improved Tf-mediated endocytosis of the AuNP, while minimizing the natural nonspecific cell interaction of Tat peptides. This system resulted in highly improved in vitro/in vivo tumor-selective uptake over AuNP bearing a single ligand (Tf or Tat peptides). Furthermore, this system resulted in significant enhancement of in vivo photothermal tumor cell ablation under light-irradiation conditions for AuNP. We believe that this design is a promising method to easily modify conventional antibodies or ligands to improve their disease-recognition ability.