Low-Power Magnetic Resonance-Guided Focused Ultrasound Tumor Ablation upon Controlled Accumulation of Magnetic Nanoparticles by Cascade-Activated DNA Cross-Linkers

Abstract

Magnetic resonance-guided focused ultrasound (MRgFUS) is a promising non-invasive surgical technique with spatial specificity and minimal off-target effects. Despite the expanding clinical applications, the major obstacles associated with MRgFUS still lie in low magnetic resonance imaging (MRI) sensitivity and safety issues. High ultrasound power is required to resist the energy attenuation during the delivery to the tumor site and may cause damage to the surrounding healthy tissues. Herein, a surface modification strategy is developed to simultaneously strengthen MRI and ultrasound ablation of MRgFUS by prolonging Fe3O4 nanoparticles’ blood circulation and tumor-environment-triggered accumulation and retention at the tumor site. Specifically, reactive oxygen species-labile methoxy polyethylene glycol and pH-responsive DNA cross-linkers are modified on the surface of Fe3O4 nanoparticles, which can transform nanoparticles into aggregations through the cascade responsive reactions at the tumor site. Notably, DNA is selected as the pH-responsive cross-linker because of its superior biocompatibility as well as the fast and sensitive response to the weak acidity of 6.5–6.8, corresponding to the extracellular pH of tumor tissues. Due to the significantly enhanced delivery and retention amount of Fe3O4 nanoparticles at the tumor site, the MRI sensitivity was enhanced by 1.7-fold. In addition, the ultrasound power was lowered by 35% to reach a sufficient thermal ablation effect. Overall, this investigation demonstrates a feasible resolution to promote the MRgFUS treatment by enhancing the therapeutic efficacy and reducing the side effects, which will be helpful to guide the clinical practice in the future.

pH-Responsive doxorubicin-loaded magnetosomes for magnetic resonance-guided focused ultrasound real-time monitoring and ablation of breast cancer

“…Magnetic resonance-guided focused ultrasound surgery (MRgFUS) offers an effective opportunity for tumor ablation as a prospering non-invasive ultrasound thermal therapy method for soft tissue sites. 3,27 Due to high accumulation and a long retention time, STPSD nanoparticles become potential sensitizers for MRgFUS applications. The MRgFUS system can monitor the temperature of the tumor and surrounding area in real time via MRI.…”

“…MR-guided focused ultrasound surgery (MRgFUS), combined with intravenously injected contrast agents, has emerged as a noninvasive thermal ablation technology for essential tremor, uterine fibroids and some solid tumors. [1][2][3][4] However, therapeutic outcomes in oncology can be improved with the precision guidance of MRgFUS which offers real-time MRI feedback for tissue monitoring and intraoperative target location. 5 Magnetic resonance imaging (MRI) that provides precision diagnostics with a high degree of spatial and temporal resolution can be a clinically promising technique in MRgFUS ablation.…”

Nano-engineering nanomedicines with customized functions for tumor treatment applications

“…In the tumor area, the labile TK-PEG layer was shed off in response to overexpressed ROS, after which DNA folded in response to tumor acidity and drove nanoparticles’ aggregation, accumulating at the tumor site, thereby enhancing magnetic resonance imaging and ultrasound ablation (Fig. 6 c) [ 139 ]. Pharmacy Department and others also designed a pH and GSH dual response nanomedicines through surface modification.…”

“…c Schematic diagram of the synthetic route of FSIC5P and the function of FSIC5P in response to ROS and pH in tumor tissues. Reproduced with permission [ 139 ]. Copyright 2022, American Chemical Society …”

Advances in Brain Tumor Therapy Based on the Magnetic Nanoparticles

“…Pre- and post-MRI results indicated that HIFU permanently destroyed the tumor. 215 In 2022, Zhang et al 216 synthesized ferromagnetic Fe 3 O 4 nanoparticles with a diameter of 70 nm. The Fe 3 O 4 nanoparticles were coated onto silica after conjugation with i-motif DNA to prepare a Fe 3 O 4 @SiO 2 /i-motif.…”