pH-Induced aggregation of gold nanoparticles for photothermal cancer therapy.

We report a "smart" gold nanoparticle that is designed to aggregate in mild acidic intracellular environments by its hydrolysis-susceptible citraconic amide surface. With a relatively small size of 10 nm, the "smart" gold nanoparticles can be efficiently internalized into cancerous cells. Triggered by pH change, the nanoparticle surfaces are engineered to have both positive and negative charges. Electrostatic attractions between the nanoparticles can rapidly form aggregates inside the cells, and the aggregates accumulate as the exocytosis is blocked by the increased size. Endocytosis of gold nanoparticles and the aggregation are monitored real-time by dark field optical microscopy. The pH-induced formation of aggregates shifts the absorption to far-red and near-infrared. The absorption shift to longer wavelength is used for photothermal cancer therapy as it guarantees maximal tissue penetration for potential therapeutic applications. The gold nanoparticles show selective and efficient destruction of cancerous cells with an intensity threshold of 5 W/cm(2) to induce the thermal destruction. In the intensity range 5-13 W/cm(2), the circular area of damaged cells increases linearly with the irradiation power density. This shows a new proof-of-concept for photothermal cancer therapy that exploits collective plasmon modes of metal nanoparticles.