Mn(II) Optimized Sono/Chemodynamic Effect of Porphyrin‐Metal–Organic Framework Nanosheets for MRI‐Guided Colon Cancer Therapy and Metastasis Suppression

Sonodynamic therapy (SDT) offers a remarkable non-invasive ultrasound (US) treatment by activating sonosensitizer and generating reactive oxygen species (ROS) to inhibit tumor growth. The development of multifunctional, biocompatible, and highly effective sonosensitizers remains a current priority for SDT. Herein, the first report that Mn(II) ions chelated Gd-TCPP (GMT) nanosheets (NSs) are synthesized via a simple reflux method and encapsulated with pluronic F-127 to form novel sonosensitizers (GMTF). The GMTF NSs produce a high yield of ROS under US irradiation due to the decreased highest occupied molecular orbital-lowest unoccupied molecular orbital gap energy (2.7-1.28 eV). Moreover, Mn(II) ions endow GMTF with a fascinating Fenton-like activity to produce hydroxyl radicals in support of chemodynamic therapy (CDT). It is also effectively used in magnetic resonance imaging (MRI) with high relaxation rate (r 1: 4.401 mM-1 s-1) to track the accumulation of NSs in tumors. In vivo results indicate that the SDT and CDT in combination with programmed cell death protein 1 antibody (anti-PD-1) show effective metastasis prevention effects, and 70% of the mice in the GMTF + US + anti-PD-1 group survived for 60 days. In conclusion, this study develops a sonosensitizer with promising potential for utilizing both MRI-guided SDT and CDT strategies.