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

Zhang, Xindan1; Lu, Hongwei1; Tang, Na2; Chen, An2; Wei, Zixiang1; Cao, Rong2; Zhu, Yi2; Lin, Li1; Li, Qing1; Wang, Zhongling2; Tian, Leilei1

2022-07-01

10.1021/acsami.2c07235

ACS Applied Materials & Interfaces   Impact Factor & Quartile

1944-8244

1944-8252

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 tumorenvironment-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.

MRgFUS Fe 3 O 4 nanoparticles i-motif DNA cascade activation tumor accumulation

SCI ; EI

English

First ; Corresponding

National Natural Science Foundation of China["51973089","81971664"] ; Shenzhen Science and Technology Innovation Commission[KQTD20170810111314625] ; Shanghai Pujiang Program[2019PJD044]

Science & Technology - Other Topics ; Materials Science

Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary

WOS:000825425600001

AMER CHEMICAL SOC

20223312579875

Ablation ; Biocompatibility ; Cardiovascular system ; Histology ; Magnetic resonance imaging ; Nanomagnetics ; Nanoparticles ; Resonance ; Tumors ; Ultrasonic applications

Biological Materials and Tissue Engineering:461.2 ; Immunology:461.9.1 ; Heat Transfer:641.2 ; Magnetism: Basic Concepts and Phenomena:701.2 ; Imaging Techniques:746 ; Ultrasonic Applications:753.3 ; Nanotechnology:761 ; Mechanics:931.1 ; Solid State Physics:933

Web of Science

1.Southern Univ Sci & Technol, Dept Mat Sci & Engn, Shenzhen 518055, Guangdong, Peoples R China
2.Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Sch Med, Dept Radiol, Shanghai 200080, Peoples R China

Zhang, Xindan,Lu, Hongwei,Tang, Na,et al. Low-Power Magnetic Resonance-Guided Focused Ultrasound Tumor Ablation upon Controlled Accumulation of Magnetic Nanoparticles by Cascade-Activated DNA Cross-Linkers[J]. ACS Applied Materials & Interfaces,2022,14(28):31677-31688.

Zhang, Xindan.,Lu, Hongwei.,Tang, Na.,Chen, An.,Wei, Zixiang.,...&Tian, Leilei.(2022).Low-Power Magnetic Resonance-Guided Focused Ultrasound Tumor Ablation upon Controlled Accumulation of Magnetic Nanoparticles by Cascade-Activated DNA Cross-Linkers.ACS Applied Materials & Interfaces,14(28),31677-31688.

Zhang, Xindan,et al."Low-Power Magnetic Resonance-Guided Focused Ultrasound Tumor Ablation upon Controlled Accumulation of Magnetic Nanoparticles by Cascade-Activated DNA Cross-Linkers".ACS Applied Materials & Interfaces 14.28(2022):31677-31688.