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

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 H₂O₂ into cytotoxic reactive oxygen species (ROS) for CDT. Moreover, the nanoreagent demonstrated dual catalytic activity, converting tumor-overexpressed H₂O₂ into oxygen (O₂) 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.