Disentangling the intrinsic relaxivities of highly purified graphene oxide

The chemistry of Contrast Agents (CAs) for Magnetic Resonance Imaging (MRI) applications is an active area of research and, in recent work, it was shown that CA-based Graphene Oxide (GO) has valuable properties for biomedical uses. GO has a potential as MRI CAs thanks to several functionalities, like its ability to penetrate tissues and cell membranes, as well as easy coupling with therapeutic agents, therefore showing the potential for both a diagnostic and therapeutic role. In this study, we performed a thorough cleaning of the GO sample (synthesized using a modified Hummers method), minimizing the amount of residual manganese down to 73 ppm. Using a wide range of physical-chemical methods (morphology, chemical composition, elemental analysis, spectroscopies, and imaging), we characterized the intrinsic longitudinal and transverse relaxivities of highly purified GO nanosheets. X-band Electron Paramagnetic Resonance (EPR) allowed to recognize the paramagnetic species involved, and 1.0 T MRI was used to disentangle the relative contributions to the MRI contrast of pristine GO nanosheets arising from structural defects and residual paramagnetic manganese impurities embedded in the nanomaterial. Although experiments show that the MRI relaxivity of GO nanosheets arises from the cumulative effect of structural defects and paramagnetic impurities, we conclude that the latter contribution to the longitudinal and transverse relaxivities becomes irrelevant for highly purified (pristine) GO. This novel finding clearly demonstrate that, apart from trivial manganese inclusion, pristine GO produces an inherent MRI response via structural defects, and therefore it is on its own a suitable candidate as MRI contrast agent.