Folic acid-targeted Mn-doped carbon dots for controlled ROS amplification and FL/MR imaging-guided synergistic Sono-Chemodynamic Cancer therapy.

Carbon dots (CDs) have emerged as promising sonosensitizers due to their biocompatibility and tunable properties, yet their clinical translation is hindered by limited catalytic efficiency and inadequate tumor-targeting capabilities. Herein, we developed folic acid-functionalized manganese-doped CDs (FA-Mn-CDs) as a multifunctional theranostic agent for fluorescence/magnetic resonance (FL/MR) dual-mode imaging-guided sonodynamic/chemodynamic therapy (SDT/CDT). Mn doping not only conferred MR contrast but also endowed FA-Mn-CDs with Fenton-like catalytic activity, enabling efficient conversion of endogenous HO into cytotoxic reactive oxygen species (ROS) for CDT. Moreover, the nanoreagent demonstrated dual catalytic activity, converting tumor-overexpressed H₂O₂ into oxygen (O) to mitigate hypoxic conditions while simultaneously enhancing ultrasound (US)-induced ROS production in SDT. In 4 T1 tumor-bearing mice, FA-Mn-CDs achieved ≥85 % suppression of primary tumor growth and pulmonary metastases, with rapid renal clearance (within 24 h) and negligible systemic toxicity. This work presents a versatile theranostic nanoplatform capable of FL/MR imaging-guided combination of SDT/CDT for precise tumor treatment.