Polyethyleneimine-assisted one-pot synthesis of quasi-fractal plasmonic gold nanocompo-sites as a photothermal theranostic agent

Gold nanoparticles have been thoroughly used in designing thermal ablative therapies and photoacoustic imaging for cancer owing to their unique and tunable plasmonic properties. While plasmonic properties highly depend on size and structure, controllable aggregation of gold nanoparticles can trigger a plasmonic coupling of adjacent electronic clouds, henceforth leading to an increase of light absorption within the near-infrared (NIR) window. Polymer-engraftment of gold nanoparticles has been investigated to obtain plasmonic coupling phenomenon, but complex chemical steps are often needed to accomplish a biomedically relevant product. An appealing and controllable manner to achieve polymer-based plasmon coupling is a template-assisted Au+3 reduction, that ensures in situ gold reduction and coalescence. Among the polymers exploited as reducing agents are polyethyleneimines (PEI). In this study, we addressed the PEI-assisted synthesis of gold nanoparticles and their further aggregation to obtain fractal NIR-absorbent plasmonic nanoaggregates for photothermal therapy and photoacoustic imaging of colorectal cancer. PEI-assisted Au+3 reduction was followed up by UV-visible light absorption, small-angle X-ray scattering (SAXS), and photo-thermal conversion. Reaction kinetic, stability, and photothermal plasmonic properties of as-synthesized nanocomposites tightly depended on PEI:Au ratio. We defined a PEI-Au ratio range (2.5-5) for one-pot synthesis of gold nanoparticles that self-arrange into fractal nanoaggregates with demonstrated photo-thermal therapeutic and imaging efficiency both in vitro and in vivo in a colorectal carcinoma (CRC) animal model.