In Situ Gastric pH Imaging with Hydrogel Capsule Isolated Paramagnetic Metallo-albumin Complexes

Abnormal gastric pH (pH > 3) has instructive significance for early diagnosis of various diseases, including cancer. However, for low patient compliance, limited penetration depth, high dependence on physiological function or unsafety issue, in situ noninvasive monitoring gastric pH is challenged. Herein, we developed a hydrogel capsule isolated human serum albumin-manganese complex (HSA-Mn) for in situ magnetic resonance imaging (MRI) gastric pH monitoring for the first time. In this strategy, the rotation motion restriction of Mn2+ after binding to HSA significantly increased the R1 (longitudinal relaxation rate) signal, and its high correlation with protonation imparted the HSA-Mn system sensitive responsiveness to varying pH (R1(pH 7)/R1(pH 1) = 8.2). Moreover, a screw jointed hydrogel capsule with signal confinement and internal standard abilities was designed. Such a nanoporous hydrogel capsule with size selectivity to surrounding molecules enabled a stable and sensitive response to different pH simulated gastric fluid within 0.5 h. In addition, with the unique structural outline and stable MRI characteristics, the capsule could also work as an internal standard, which facilitates the collection of signals and trace of the capsule in vivo. Through validating in a rabbit model, the precise abnormal gastric pH recognition capacity of the HSA-Mn hydrogel capsule was amply confirmed. Hence, the hydrogel capsule isolated HSA-Mn system strategy with great biocompatibility could be expected to be a potent tool for in situ anti-disturbance MRI of gastric pH in future clinical application.