Covalent Organic Framework Nanobowls as Activatable Nanosensitizers for Tumor-Specific and Ferroptosis-Augmented Sonodynamic Therapy.

Covalent organic frameworks (COFs) have attracted increasing attention for biomedical applications. COFs-based nanosensitizers with uniform nanoscale morphology and tumor-specific curative effects are in high demand; however, their synthesis is yet challenging. In this study, distinct COF nanobowls are synthesized in a controlled manner and engineered as activatable nanosensitizers with tumor-specific sonodynamic activity. High crystallinity ensures an ordered porous structure of COF nanobowls for the efficient loading of the small-molecule sonosensitizer rose bengal (RB). To circumvent non-specific damage to normal tissues, the sonosensitization effect is specifically inhibited by the in situ growth of manganese oxide (MnOx ) on RB-loaded COFs. Upon reaction with tumor-overexpressed glutathione (GSH), the "gatekeeper" MnOx is rapidly decomposed to recover the reactive oxygen species (ROS) generation capability of the COF nanosensitizers under ultrasound irradiation. Increased intracellular ROS stress and GSH consumption concomitantly induce ferroptosis to improve sonodynamic efficacy. Additionally, the unconventional bowl-shaped morphology renders the nanosensitizers with enhanced tumor accumulation and retention. The combination of tumor-specific sonodynamic therapy and ferroptosis achieves high efficacy in killing cancer cells and inhibiting tumor growth. This study paves the way for the development of COF nanosensitizers with unconventional morphologies for biomedicine, offering a paradigm to realize activatable and ferroptosis-augmented sonodynamic tumor therapy.

Evaluation of Microwave Ablation in 4T1 Breast Tumor by a Novel VEFGR2 Targeted Ultrasound Contrast Agents.

OBJECTIVES: A novel ultrasound contrast agent (UCA) VEGFR2-targeting iron-doped silica (SiO2) hollow nanoparticles (VEGFR2-PEG-HSNs-Fe NPs) was prepared and applied in microwave ablation for breast cancer to investigate its value in the evaluation of effectiveness after tumor ablation. METHODS: VEGFR2-PEG-HSNs-Fe NPs were prepared by using nano-SiO2, which was regarded as a substrate and etched by ferrous acetate, and then modified with anti-VEGFR2 antibody. Laser confocal microscope and flow cytometry were used to observe its main physicochemical properties, and biological safety was also investigated. After the xenograft tumor was treated with microwave ablation, the extent of perfusion defect was evaluated by ultrasound by injecting VEGFR2-PEG-HSNs-Fe NPs. RESULTS: The average particle size of VEGFR2-PEG-HSNs-Fe was 276.64 ± 30.31 nm, and the surface potential was -13.46 ± 2.83 mV. In vitro, the intensity of ultrasound signal increased with UCA concentration. Good biosafety was performed in in vivo and in vitro experiments. The enhanced ultrasound signal was detected in tumors after injection of VEGFR2-PEG-HSNs-Fe NPs, covering the whole tumor. The lesions, which were incompletely ablated, presented as contrast agent perfusion at the periphery of the tumor, and contrast enhanced ultrasound (CEUS) was performed again after complementary ablation. It was confirmed that all the lesions were completely ablated. CONCLUSION: Nano-targeted UCAs VEGFR2-PEG-HSNs-Fe NPs had good biosafety and ability of specific imaging, which might be used as a contrast agent in CEUS to evaluate the efficacy of tumor ablation.