Coupling graphene with a soft polymer surface offers the possibility to build hybrid constructs with new electrical, optical, and mechanical properties. However, the low reactivity of graphene is a hurdle in the synthesis of such systems which is often bypassed by oxidizing its carbon planar structure. However, the defects introduced with this process jeopardize the properties of graphene. In this paper we present a different approach, applicable to many different polymer surfaces, which uses surfactant assisted ultrasonication to exfoliate, and simultaneously suspend, graphene in water in its intact form. Tethering pristine graphene sheets to the surfaces is accomplished by using suitable reactive functional groups of the surfactant scaffold. We focused on applying this approach to the fabrication of a hybrid system, made of pristine graphene tethered to poly(vinyl alcohol) based microbubbles (PVA MBs), designed for enhancing photoacoustic signals. Photoacoustic imaging (PAI) is a powerful preclinical diagnostic tool which provides real time images at a resolution of 40 μm. The leap toward clinical imaging has so far been hindered by the limited tissues penetration of near-infrared (NIR) pulsed laser radiation. Many academic and industrial research laboratories have met this challenge by designing devices, each with pros and cons, to enhance the photoacoustic (PA) signal. The major advantages of the hybrid graphene/PVA MBs construct, however, are (i) the preservation of graphene properties, (ii) biocompatibility, a consequence of the robust anchoring of pristine graphene to the bioinert surface of the PVA bubble, and (iii) a very good enhancement in a NIR spectral region of the PA signal, which does not overlap with the signals of PA active endogenous molecules such as hemoglobin.

The polyelectrolyte microcapsules that can be accurate either visualized in biological media or in tissue would enhance their further in vivo application both as a carrier of active payloads and as a specific sensor. The immobilization of active species, for instance fluorescent dyes, quantum dots, metal nanoparticles, in polymeric shell enables visualization of capsules by optical imaging techniques in aqueous solution. However, for visualization of capsules in complex media an instrument with high contrast modality requires. Herein, we show for the first time photoacoustic imaging (PAI) of multifunctional microcapsules in water and in blood. The microcapsules exhibit greater photoacoustic intensity compare to microparticles with the same composition of polymeric shell presumably their higher thermal expansion. Photoacoustic intensity form microcapsules dispersed in blood displays an enhancement (2-fold) of signal compare to blood. Photoacoustic imaging of microcapsules might contribute to non-invasive carrier visualization and further their in vivo distribution.

No abstract

The ORCID identification number(s) for the author(s) of this article can be found under https://doi.

Introduction The aim of this study is to develop new strategies for the exploration of relevant preclinical lung tumor models dedicated to onco-pharmacology studies in mice. Here we refine a translational approach while overcoming physical ultrasound (US) imaging limitations allowing lung tumors exploration. Our data were compared to Computed Tomography (CT) and Bioluminescence (BLI) aiming to validate this promising approach. Methods Human lung cancer cells NCI-H460-luc2 were orthotopically xenografted in Balb/c nude mice. BLI was performed 7 days after implantation then once a week until the end of the study (Day 28) using an IVIS-Lumina II (Perkin Elmer). Tumors were imaged with the Vevo®LAZR System (FUJIFILM VisualSonics Inc.), 3D scans of US, Contrast Enhanced Ultrasound (CEUS) (Vevo MicroMarkerTM) and photoacoustic (PA) image being recorded digitally. A comparison between in vivo US and CT was achieved with additional ex vivo weight and volumetric measurements. Results The control of the tumor cell implantation was determined by BLI allowing the early quantification of tumor burden. 3D US measurements made possible longitudinal tumor volumes assessment. Compared to the other in vivo measurements, results clearly indicated the gross correlation of volumes processed with US and CT (R2 = 0.75). Such a correlation is also observed with ex vivo US weight and volumetric measurements (R2 = 0.72, R2 = 0.75 and R2 = 0.65 respectively). PA imaging evidenced the hemoglobin saturation with oxygen inside tumors, and targeted CEUS imaging allowed assessing the relative VEGFR2 expression in lung tumors. Conclusions This study proved the ability of US imaging to detect and control the in vivo orthotopic lung tumor growth. This real-time approach is fast while being completely inert regarding the in situ proliferation, as compared to dosimetry related to repeated CT examinations. Furthermore it allows overcoming the limitation of BLI at the time tumors become hypoxic since the luciferase/luciferin reaction is strictly dependent upon O2 and ATP. We described here a PA and US imaging strategy to follow the orthotopic lung tumors growth and consider biomarkers such as VEGFR2 expression or hypoxia in vivo for the first time. This procedure would be of great interest to longitudinally investigate tumor proliferation in animals when evaluating new anticancer therapies efficacy, avoiding any perturbation of the tumor progression compared to other available imaging modalities. Citation Format: Florian Raes, Julien Sobilo, Sharuja Natkunarajah, Philippe Trochet, Dieter Fuchs, Stephanie Lerondel, Alain Le Pape. Novel imaging strategy to assess the antitumor efficacy of treatments in an orthotopic mouse lung cancer model using ultrasound and photoacoustic imaging. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4200.