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

• Published in: Small (Weinheim an der Bergstrasse, Germany) Germany), 2024-04, Vol.20 (15), p.e2306364-n/a
• Main Authors: Hang, Lifeng, Li, Meng, Zhang, Yuxuan, Li, Wuming, Fang, Laiping, Chen, Yiyu, Zhou, Chunze, Qu, Hong, Shao, Lianyi, Jiang, Guihua
• Format: Article
• Language: English
• Subjects: Animals; Antibodies; Biocompatibility; Cell death; Cell Line, Tumor; chemodynamic therapy; colon cancer; Colonic Neoplasms - diagnostic imaging; Colonic Neoplasms - drug therapy; Gadolinium; Hydroxyl radicals; Ions; Magnetic Resonance Imaging; Metal-Organic Frameworks; Metastasis; metastasis suppression; Mice; Molecular orbitals; Nanosheets; Neoplasms; Porphyrins; Porphyrins - pharmacology; Porphyrins - therapeutic use; Reactive Oxygen Species; sonodynamic therapy; Therapy; Tumors; Ultrasonic Therapy
• ISSN: 1613-6810; 1613-6829
• DOI: 10.1002/smll.202306364

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. Mn(II) ions chelated porphyrin based metal‐organic framework nanosheets (MOF NSs) results in a superior reactive oxygen species yield under ultrasound irradiation. In addition, these MOF NSs with a fascinating Fenton‐like activity to produce hydroxyl radicals for chemodynamic therapy. The sonodynamic therapy and chemodynamic therapy in combination with programmed cell death protein 1 antibody are effectively inhibited tumor metastasis and greatly prolonged the survival of mice.