**Assessment of the Theranostic Potential of Gold Nanostars—A Multimodal Imaging and Photothermal Treatment Study**

**Antoine D'Hollander 1,2,3, Greetje Vande Velde 1,2, Hilde Jans 3, Bram Vanspauwen 3, Elien Vermeersch 1,2, Jithin Jose 4, Tom Struys 5, Tim Stakenborg 3, Liesbet Lagae 3,6 and Uwe Himmelreich 1,2,\***


Received: 31 August 2020; Accepted: 21 October 2020; Published: 23 October 2020

**Abstract:** Gold nanoparticles offer the possibility to combine both imaging and therapy of otherwise difficult to treat tumors. To validate and further improve their potential, we describe the use of gold nanostars that were functionalized with a polyethyleneglycol-maleimide coating for in vitro and in vivo photoacoustic imaging (PAI), computed tomography (CT), as well as photothermal therapy (PTT) of cancer cells and tumor masses, respectively. Nanostar shaped particles show a high absorption coefficient in the near infrared region and have a hydrodynamic size in biological medium around 100 nm, which allows optimal intra-tumoral retention. Using these nanostars for in vitro labeling of tumor cells, high intracellular nanostar concentrations could be achieved, resulting in high PAI and CT contrast and effective PTT. By injecting the nanostars intratumorally, high contrast could be generated in vivo using PAI and CT, which allowed successful multi-modal tumor imaging. PTT was successfully induced, resulting in tumor cell death and subsequent inhibition of tumor growth. Therefore, gold nanostars are versatile theranostic agents for tumor therapy.

**Keywords:** gold nanostars; photothermal therapy; photoacoustic imaging; computed tomography; nanoparticles; cancer; theranostic agents
