Siloxane Nanoprobes for Labeling and Dual Modality Functional Imaging of Neural Stem Cells

Abstract

Cell therapy represents a promising therapeutic for a myriad of medical conditions, including cancer, traumatic brain injury, and cardiovascular disease among others. A thorough understanding of the efficacy and cellular dynamics of these therapies necessitates the ability to non-invasively track cells in vivo. Magnetic resonance imaging (MRI) provides a platform to track cells as a non-invasive modality with superior resolution and soft tissue contrast. We recently reported a new nanoprobe platform for cell labeling and imaging using fluorophore doped siloxane core nanoemulsions as dual modality (1H MRI/Fluorescence), dual-functional (oximetry/detection) nanoprobes. Here, we successfully demonstrate the labeling, dual-modality imaging, and oximetry of neural progenitor/stem cells (NPSCs) in vitro using this platform. Labeling at a concentration of 10 μl/104 cells with a 40%v/v polydimethylsiloxane core nanoemulsion, doped with rhodamine, had minimal effect on viability, no effect on migration, proliferation and differentiation of NPSCs and allowed for unambiguous visualization of labeled NPSCs by 1H MR and fluorescence and local pO2 reporting by labeled NPSCs. This new approach for cell labeling with a positive contrast 1H MR probe has the potential to improve mechanistic knowledge of current therapies, and guide the design of future cell therapies due to its clinical translatability.

More bullets for PISTOL: linear and cyclic siloxane reporter probes for quantitative 1H MR oximetry

“…Based on initial observations at 4.7 T, the promising pO 2 reporter OMTSO was further evaluated at higher fields (7 T and 9.4 T) and calibration curves were characterized as a function of temperature. Finally, given the prior application of PDMSO at 7 T for cell labelling and oximetry 46 , its calibration curve at 7 T was characterized as a function of temperature.…”

“…Exploiting the same concept, our group has previously shown the feasibility of accurate and repeated measurements of oxygen using hexamethyldisiloxane (HMDSO) in thigh muscle and tumor regions in vivo using 1 H MR oximetry 38,39 . We have also shown the ability of siloxane based nanoemulsions for tissue oximetry 44 as well as cellular oximetry 45,46 . Siloxanes can be synthesized in a variety of forms (linear or cyclic, increasing chain length, with or without functional groups) and have been used in various applications such as biomedicine, cosmetics, and food processing 47 .…”

A faster PISTOL for 1H MR‐based quantitative tissue oximetry

“…An acquisition time of 1.5 minutes was reported using the SNAP‐IR sequence, compared with 6.5 minutes for the fluorocarbon relaxometry using echo planar imaging for dynamic oxygen mapping (FREDOM) sequence while maintaining a similar in‐plane spatial resolution. PISTOL‐LL can thus facilitate fast and dynamic pO 2 mapping in various tracking and cellular labeling applications, such as those in neural stem cells, in both 19 F and 1 H oximetry studies involving dual‐modality MRI‐fluorescence probes . Given the speed of acquisition, the PISTOL‐LL sequence can be easily incorporated into existing clinical protocols, thus providing a valuable tool for fast quantitative oximetry.…”

“…The normal functioning of various tissues and organs in the human body is dependent on the efficient delivery of oxygen. Tissue oximetry techniques are increasingly playing an important role in the assessment and monitoring of various pathologies such as in traumatic brain injury, ischemic stroke, wound healing, in cellular tracking and imaging the health of labeled cells, resuscitation approaches in critical organ beds, and for monitoring oxygen dynamics in cancer . Numerous factors can cause tissue to develop hypoxic (low oxygen tension, pO 2 ) regions such as impaired perfusion, breakdown in diffusion processes, reduced oxygen transport functionality of blood in conditions like anaemia, increased cellular cytotoxicity, and low blood pO 2 commonly seen in pulmonary diseases .…”

“…One can subsequently use PISTOL to map the tissue pO 2 at various locations where siloxanes (neat or emulsified) have been exogenously administered or accumulated after endogenous administration. This sequence can also be used to record the dynamic changes in the tissue pO 2 in response to intervention or for imaging and oximetry of siloxane‐labeled cells …”