In vivo volumetric photoacoustic molecular angiography and therapeutic monitoring with targeted plasmonic nanostars

Abstract

Photoacoustic (PA) imaging promises deeper tissue penetration while maintaining rich optical contrast as compared to other high resolution optical imaging techniques. In this report, a near-infrared pulse laser serves as the excitation source, and 128 ultrasonic transducers are spirally distributed on a hemispherical surface to receive PA signals for three-dimensional (3D) image reconstruction. With these attributes, the unique modality produces an isotropic and homogeneous spatial resolution (∼200 μm) with penetration depth of centimeters. Cyclic Arg-Gly-Asp (RGD) peptides conjugated plasmonic gold nanostars (RGD-GNS) are designed to specifically target over-expressed integrin α(v)β₃ on tumor neovasculature, enabling highly sensitive angiography and photothermal therapy (PTT). After the administration of RGD-GNS, tumor angiogenesis is clearly imaged with enhanced contrast, and the growth of tumor is effectively inhibited by PTT after laser irradiation. This study suggest that the PA angiography with plasmonic RGD-GNS can be applied as a triple functional platform for tumor diagnosis, PTT, and treatment monitoring. This PA technique offers deeper imaging depth with homogeneous resolution over existing optical imaging techniques for early diagnosis of tumor angiogenesis as well as on-the-spot nanotherapeutic evaluation.

Keywords: photoacoustic imaging; photothermal therapy; plasmonic nanostars; therapy monitoring; tumor angiogenesis.