Ultrastable calixarene-coated gold nanorods as promising candidates for contrast agents in photoacoustic imaging

Victor Lepeintre1,2, Gilles Bruylants1, Ivan Jabin2

1 Engineering of Molecular NanoSystems, ULB
2 Laboratoire de Chimie Organique, ULB


Gold nanorods (AuNRs) have emerged as extremely promising material for the development of biomedical in vivo applications. In addition to the already outstanding properties of gold nanoparticles, such as good biocompatibility or the existence of various well-established surface chemistries, AuNRs present easily tunable optical properties. Indeed, they display two distinct LSPR bands, a transverse and a longitudinal one, whose maximum absorbance wavelength can be tuned through the aspect ratio of the rod. For high aspect ratios, the longitudinal band lies in the near-infrared (NIR) region, which is often referred as the “optical tissue transparency window” as absorbance by water, hemoglobin and other endogenous molecules is minimal in that region, leading to increased light penetration in tissues. Gold is also one of the most chemically inert metals and has a high electron density: it is therefore possible to locate gold nanostructures in complex environments, such as tissues, making them ideal candidates as bioimaging contrast agents. Photoacoustic imaging has recently emerged as one of the most promising imaging techniques that combines the high contrast of optical imaging with the spectral and temporal resolution of ultrasound. It is a “light in/sound out” technique compared to the conventional “sound in/sound out” ultrasound technique. AuNRs possess several qualities that make them excellent photoacoustic contrast agents: they have a high biocompatibility, long circulation times, and intense optical absorption cross-sections and extinction coefficients in the NIR region which, as already stated, allows a deeper tissue penetration with a lower background absorption than visible light. However, one limitation of the AuNRs is their anisotropic structure that is susceptible to deformation upon illumination: pulsed-laser irradiation has been shown to lead to the spherification of AuNRs, leading to a rapid decrease of their NIR absorption.

An efficient strategy for the building of robust and thin organic coatings on various surfaces consists in the use of calix[4]arene-tetradiazonium salts. Indeed, these molecular platforms can be irreversibly and strongly grafted on surfaces through the reduction of their diazonium groups. We have adapted this calixarene-based coating technology to produce ultrastable AuNRs (AuNRs-calix), more stable than conventional AuNRs. These calixarene-coated AuNRs were then used as contrast agents in photoacoustic imaging. Our preliminary results indicate that these AuNRs-calix remain stable for longer periods of time under pulsed laser irradiation than commonly used AuNRs coated with citrate or thiols. Increasing the stability of AuNRs under laser irradiation, allowing longer analysis time, could lead to significant advances in the field.