• • The Mn-CaCO3@NGQDs/PAA nanoplatform generates substantial ROS under ultrasound, with singlet oxygen (1O2) production confirmed, enhancing SDT efficacy despite tumor antioxidant defenses.
• • Acidic tumor microenvironment triggers sustained Ca2+ release, inducing calcium overload that synergistically amplifies oxidative stress, leading to effective tumor growth suppression.
• • The nanoplatform demonstrates dual-mode T1/T2-weighted MRI performance, facilitating precise tumor localization and image-guided therapy.
• • In vivo studies at a high injection dosage of 10 mg kg−1 showed no significant alterations in hematological, hepatic, or renal indicators, confirming satisfactory biocompatibility and biosafety.