Precise Cancer Anti-acid Therapy Monitoring Using pH-Sensitive MnO₂@BSA Nanoparticles by Magnetic Resonance Imaging.

Area of Science:

• Biomedical Imaging
• Nanotechnology
• Oncology

Background:

• Tumor microenvironments exhibit pH gradients, fostering aggressive and treatment-resistant cancer cells.
• Accurate, noninvasive quantification of dynamic pH changes during cancer therapy is crucial for prognosis and efficacy assessment.
• Current methods for dynamic pH monitoring in tumors are challenging.

Purpose of the Study:

• To develop and utilize pH-sensitive magnetic resonance imaging (MRI) contrast agents for visualizing and quantifying acid-base changes in solid tumors during anti-acid treatment.
• To assess the potential of MRI with pH-sensitive nanoparticles to monitor tumor microenvironment pH dynamics noninvasively.

Main Methods:

• Development of manganese dioxide@bovine serum albumin (MnO₂@BSA) nanoparticles as pH-sensitive MRI contrast agents.
• In vivo MRI of NCI-H460 lung tumors in mice treated with the anti-acid drug esomeprazole.
• Validation of MRI findings using a pH microsensor, immunofluorescence, Western blot, and ELISA assays.

Main Results:

• MnO₂@BSA nanoparticles effectively amplified MR contrast in response to the acidic tumor extracellular environment.
• MRI with MnO₂@BSA nanoparticles successfully visualized spatiotemporal pH fluctuations during esomeprazole treatment.
• MRI-detected pH changes correlated with pH microsensor measurements (pH 6.12-6.63) and confirmed esomeprazole's inhibition of V-ATPase in cancer cells.

Conclusions:

• MnO₂@BSA-based MRI provides a noninvasive method for real-time monitoring of dynamic pH fluctuations in solid tumors.
• This approach facilitates the detection of acidic tumor microenvironments and aids in evaluating anti-acid therapeutic efficacy.
• The developed MRI technique shows significant potential for dynamic in vivo pH monitoring without requiring invasive microsensors.