Graphene Oxide Enhances Cellular Delivery of Hydrophilic Small Molecules by Co-incubation

The delivery of bioactive molecules into cells has broad applications in biology and medicine. Polymer-modified graphene oxide (GO) has recently emerged as a <i>de facto</i> noncovalent vehicle for hydrophobic drugs. Here, we investigate a different approach using native GO to deliver hydrophilic molecules by co-incubation in culture. GO adsorption and delivery were systematically studied with a library of 15 molecules synthesized with Gd(III) labels to enable quantitation. Amines were revealed to be a key chemical group for adsorption, while delivery was shown to be quantitatively predictable by molecular adsorption, GO sedimentation, and GO size. GO co-incubation was shown to enhance delivery by up to 13-fold and allowed for a 100-fold increase in molecular incubation concentration compared to the alternative of nanoconjugation. When tested in the application of Gd(III) cellular MRI, these advantages led to a nearly 10-fold improvement in sensitivity over the state-of-the-art. GO co-incubation is an effective method of cellular delivery that is easily adoptable by researchers across all fields

Mechanisms of Gadographene-Mediated Proton Spin Relaxation

Gd­(III) associated with carbon nanomaterials relaxes water proton spins at an effectiveness that approaches or exceeds the theoretical limit for a single bound water molecule. These Gd­(III)-labeled materials represent a potential breakthrough in sensitivity for Gd­(III)-based contrast agents used for magnetic resonance imaging (MRI). However, their mechanism of action remains unclear. A gadographene library encompassing GdCl₃, two different Gd­(III) complexes, graphene oxide (GO), and graphene suspended by two different surfactants and subjected to varying degrees of sonication was prepared and characterized for their relaxometric properties. Gadographene was found to perform comparably to other Gd­(III)–carbon nanomaterials; its longitudinal (<i>r</i>₁) and transverse (<i>r</i>₂) relaxivity are modulated between 12–85 mM^–1 s^–1 and 24–115 mM^–1 s^–1, respectively, depending on the Gd­(III)–carbon backbone combination. The unusually large relaxivity and its variance can be understood under the modified Florence model incorporating the Lipari–Szabo approach. Changes in hydration number (<i>q</i>), water residence time (τ_M), molecular tumbling rate (τ_R), and local motion (τ_fast) sufficiently explain most of the measured relaxivities. Furthermore, results implicated the coupling between graphene and Gd­(III) as a minor contributor to proton spin relaxation