Modification of nanodiamonds for fluorescence bioimaging.

Non-invasive bioimaging is essential in enhancing pre-clinical diagnosis and therapy. Developing efficient imaging probes with high stability, low toxicity, and the potential of offering high resolution images is a very important aspect of developing non-invasive bioimaging techniques. Fluorescent nanodiamonds, which are produced by high energy beam irradiation and high temperature/pressure treatment, have been extensively investigated. In this study, we report the chemical modification of common nanodiamonds (prepared by detonation and high-pressure high-temperature milling) using a stable fluorophore (perylene diimide derivative) via carbodiimide coupling. The resulting nanodiamonds show good biocompatibility, cellular uptake and fluorescent imaging potential with mesenchymal stromal cells. This method provides an efficient alternative approach to the preparation and the use of fluorescent nanodiamonds for bioimaging, with the potential benefit of chemically adjusting the structure of perylene diimide for optimized emission/absorbance wavelength.

Evaluation of Cytotoxicity and Bioimaging of Nitrogen-Vacancy Nanodiamonds.

Nanodiamonds, due to their chemical inertness and biocompatibility, have found extensive uses in drug delivery and biomedical applications. Fluorescent nanodiamonds with fluorescent properties generated by nitrogen-vacancy defects have been intensively investigated for bioimaging, due to their high quantum yield and high photobleaching stability. In addition, the surface properties and particle size of nanodiamonds have significant impacts on cellular uptake and imaging quality. In this study, nitrogen-vacancy nanodiamonds with different particle sizes (40 nm and 90 nm) have been physicochemically characterised and investigated for their cytotoxicity and potential in fluorescence imaging. The nanodiamonds (with concentrations up to 100 µg/mL) showed cell viability >70% with mesenchymal stromal cells. The number of nanodiamonds was observed to have a larger impact on cell viability than the mass of nanodiamonds. Larger nanodiamonds (90 nm) exhibited a lower level of cytotoxicity, higher cellular uptake and fluorescence intensity. The results indicate the potential of using fluorescent nanodiamonds as a nanoprobe for effective bioimaging and cell tracking.

Perylene Diimide Nanoprobes for In Vivo Tracking of Mesenchymal Stromal Cells Using Photoacoustic Imaging.

Noninvasive bioimaging techniques are critical for assessing the biodistribution of cellular therapies longitudinally. Among them, photoacoustic imaging (PAI) can generate high-resolution images with a tissue penetration depth of ∼4 cm. However, it is essential and still highly challenging to develop stable and efficient near-infrared (NIR) probes with low toxicity for PAI. We report here the preparation and use of perylene diimide derivative (PDI) with NIR absorbance (around 700 nm) as nanoprobes for tracking mesenchymal stromal cells (MSCs) in mice. Employing an in-house synthesized star hyperbranched polymer as a stabilizer is the key to the formation of stable PDI nanoparticles with low toxicity and high uptake by the MSCs. The PDI nanoparticles remain within the MSCs as demonstrated by in vitro and in vivo assessments. The PDI-labeled MSCs injected subcutaneously on the flanks of the mice are clearly visualized with PAI up to 11 days postadministration. Furthermore, bioluminescence imaging of PDI-labeled luciferase-expressing MSCs confirms that the administered cells remain viable for the duration of the experiment. These PDI nanoprobes thus have good potential for tracking administered cells in vivo using PAI.