MRI-detectable pH nanosensors incorporated into hydrogels for in vivo sensing of transplanted cell viability

Biocompatible nanomaterials and hydrogels have become an important tool for improving cell-based therapies by promoting cell survival and protecting cell transplants from immune rejection. Although their potential benefit has been widely evaluated, it is currently not possible to determine, in vivo, if and how long cells remain viable following their administration without the use of a reporter gene. We here report a pH nanosensor-based magnetic resonance imaging (MRI) technique that can monitor cell death in vivo non-invasively. We demonstrate that specific MRI parameters that change upon cell death of microencapsulated hepatocytes are associated with the measured bioluminescence imaging (BLI) radiance. Moreover, the readout from this pH-sensitive nanosensor can be directly co-registered with high-resolution anatomical images. All the components of these nanosensors are clinical-grade and hence this approach should be a translatable and universal modification of hydrogels.