Real-time magnetic resonance visualization of tumor acidosis as a precognition indicator of therapeutic efficacy.

Abstract

Traditional antitumor strategies often require sufficient time to assess the effectiveness according to changes in tumor structure. Once ineffective, patients may miss the critical window for pursuing alternative treatment options. Herein, a manganese sulfide nanoplatform loaded with proton pump inhibitor (PPI) is developed. This nanoplatform is designed for visualizing tumor acidosis degree by magnetic resonance imaging (MRI), achieving real-time therapeutic efficacy precognition. The nanoplatform releases PPI, H₂S, and Mn²⁺ within the acidic lysosome of tumor cells. PPI inhibits V-ATPase expression, leading to an increase in intracellular H⁺ levels. H₂S accelerates glucose consumption of tumor cells, producing more lactic acid and further inducing tumor acidosis. Tumor acidosis in turn accelerates the nanoplatform's degradation, achieving higher tumor MRI. As the tumor acidosis degree correlates positively with tumor regression, real-time visualization of acidosis degree effectively predicts future therapeutics. Interestingly, tumor acidosis achieves efficient tumor metastasis suppression rather than increases it. Overall, this work presents a nanoplatform capable of visualizing tumor acidosis in real-time and precisely predicting future therapeutics.