Augmented tumor accumulation and photothermal ablation using gold nanoparticles with a particular cellular entry orientation

Gold nanoparticles with various functionalities have served as potential tools in nanotechnology for tumor ablation. In this work, we seek to design and develop gold nanoparticle with poly(ethylene glycol)-containing dopamine (hereafter termed as AuND), and to synthesize the AuND with one-sided Tat peptide expression (OT@AuND). We demonstrate the tumor cell-targeting ability on the basis of anti-nonspecific cell binding of OT@AuND and determine how the chemically modified gold nanoparticle–based product affects photothermal tumor therapy in vitro and in vivo. The OT@AuND with a particular cellular entry orientation–induced delayed endocytosis, which is advantageous for enhanced permeability and retention effect-based tumor accumulation. This is because the slower cellular interaction of OT@AuND allows it to have the time to be transported to and bind to the tumor site. In tumor cell lines, OT@AuND showed a lower cellular uptake than gold nanoparticles with full-sided Tat peptide expression (FT@AuND) in the early period (after its in vitro and in vivo administration), but the cellular internalization rate of OT@AuND caught up with that of FT@AuND in the late period. Importantly, the delayed cellular internalization feature of OT@AuND resulted in efficient tumor accumulation in tumor-bearing mice, because the time interval provided OT@AuND more chances not to bind to any cells, but to enter tumor cells, leading to selective photothermal tumor ablation. These data suggest that gold nanoparticles with a particular cellular entry orientation can be further explored as a potential photothermal therapeutic agent and as a strategy to treat tumors.