Site Selective Nucleation and Size Control of Gold Nanoparticle Photothermal Antennae on the Pore Structures of a Virus and Confined Drug Delivery

In this article, we show that the surface of the bacteriophage Qβ is equipped with natural ligands for the synthesis of small gold nanoparticles. By exploiting disulfides in the protein secondary structure and the geometry formed from the capsid quaternary structure, we find we can produce regularly arrayed patterns of ~6 nm gold nanoparticles across the surface of the virus-like particle. Experimental and computational analysis provide insight into the formation and stability of this composite. We further show that the entrapped genetic material can hold upwards of 500 molecules of the anti-cancer drug Doxorubicin without leaking and without interfering with the synthesis of the gold nanoparticles. This direct nucleation of nanoparticles on the capsid allows for exceptional conduction of photothermal energy upon nanosecond laser irradiation. As a proof of principle, we demonstrate that this energy is capable of rapidly releasing the drug from the capsid without heating the bulk solution, allowing for highly targeted cell killing in vitro.