Gas-Stabilizing Sub-100 nm Mesoporous Silica Nanoparticles for Ultrasound Theranostics

Abstract

Recent studies have demonstrated that gas-stabilizing particles can generate cavitating micron-sized bubbles when exposed to ultrasound, offering excellent application potential, including ultrasound imaging, drug delivery, and tumor ablation. However, the majority of the reported gas-stabilizing particles are relatively large (>200 nm), and smaller particles require high acoustic pressures to promote cavitation. Here, this paper reports the preparation of sub-100 nm gas-stabilizing nanoparticles (GSNs) that can initiate cavitation at low acoustic intensities, which can be delivered using a conventional medical ultrasound imaging system. The highly echogenic GSNs (F127-hMSN) were prepared by carefully engineering the surfaces of ∼50 nm mesoporous silica nanoparticles. It was demonstrated that the F127-hMSNs could be continuously imaged with ultrasound in buffer or biological solutions or agarose phantoms for up to 20 min. Also, the F127-hMSN can be stored in phosphate-buffered saline for at least a month with no loss in ultrasound responsiveness. The particles significantly degraded when diluted in simulated body fluids, indicating possible biodegradation of the F127-hMSNs in vivo . Furthermore, at ultrasound imaging conditions, F127-hMSNs did not cause detectable cell death, supporting the potential safety of these particles. Finally, strong cavitation activity generation by the F127-hMSNs under high-intensity focused ultrasound insonation was demonstrated and applied to effectively ablate cancer cells.

Progress in Mesoporous Silica Nanoparticles as Drug Delivery Agents for Cancer Treatment

“…The MSNs were stabilized by gas that can initiate cavitation at low and high acoustic intensity. They reported that under low acoustic pressure, ultrasound imaging was produced, while at high acoustic pressure, the microbubbles collapsed, which produced shockwaves and ablate the nearby cells or transiently perforate their membranes [ 234 ]. Lee and colleagues reported on multifunctional MSNs as imaging agents and carriers for photothermal therapy of cancer.…”

Gas-stabilizing nanoparticles for ultrasound imaging and therapy of cancer

“…The micron-sized bubbles generated by GSNs can backscatter the ultrasound waves and improve the contrast of ultrasound images [ 34 , 35 , 39 ]. In addition, the violent collapse of these bubbles can induce mechanical effects (e.g., shock waves and water jets) in the tissue, which are useful for improving the outcomes of ultrasound-based therapies such as tumor ablation or localized drug delivery [ 37 , 40 , 46 , 47 ].…”

“…Following these pioneering studies, several GSNs have been developed using different materials, including mesoporous silica, porous silicon, gold, and polymers (Fig. 3 ) [ 34 – 36 , 39 – 41 , 44 , 46 – 49 , 70 , 73 , 78 – 87 ]. While, as discussed in the previous section, the exact mechanism of cavitation inception by GSNs is yet to be understood, these studies found that a hydrophobic surface or cavity is required to prepare GSNs with high acoustic activity (i.e., cavitation inception at low acoustic intensities).…”

“…These solid nanoparticles are engineered to stabilize gas-pockets on their surfaces or inside their hydrophobic cavities, which can act as heterogeneous nucleation sites to produce micron-sized cavitating bubbles under ultrasound insonation [ 13 , 38 ]. Recent studies showed that nanoscale GSNs with sizes down to 50 nm could be easily prepared as they do not have a fluorocarbon component [ 39 ]. Their fluorocarbon-free nature also provides them with exceptional signal stability during ambient storage for months and in vivo for several days after intravenous injection [ 34 , 39 , 40 ].…”

“…Recent studies showed that nanoscale GSNs with sizes down to 50 nm could be easily prepared as they do not have a fluorocarbon component [ 39 ]. Their fluorocarbon-free nature also provides them with exceptional signal stability during ambient storage for months and in vivo for several days after intravenous injection [ 34 , 39 , 40 ]. In addition, GSNs have been found to generate a stronger and more durable cavitation activity than nanodroplets or microbubbles, making them highly attractive for cancer theranostics applications [ 37 , 41 – 43 ].…”