Hollow iron-silica nanoshells for enhanced high intensity focused ultrasound

Abstract

Background High intensity focused ultrasound (HIFU) is an alterative ablative technique currently being investigated for local treatment of breast cancer and fibroadenomas. Current HIFU therapies require concurrent MRI monitoring. Biodegradable 500 nm perfluoropentane (PFP) filled iron-silica nanoshells have been synthesized as a sensitizing agent for HIFU therapies, which aid both mechanical and thermal ablation of tissues. In low duty cycle high-intensity applications, rapid tissue damage occurs from mechanical rather than thermal effects, which can be monitored closely by ultrasound obviating the need for concurrent MRI. Materials and Methods Iron-silica nanoshells were synthesized by a sol-gel method on polystyrene templates and calcined to yield hollow nanoshells. The nanoshells were filled with PFP and injected directly into excised human breast tumor, and intravenously (IV) into healthy rabbits and Py8119 tumor bearing nu/nu mice. HIFU was applied at 1.1 MHz and 3.5 MPa at a 2% duty cycle to achieve mechanical ablation. Results Ex vivo in excised rabbit livers, the time to visually observable damage with HIFU was 20 seconds without nanoshells and only 2 seconds with nanoshells administered IV prior to sacrifice. Nanoshells administered IV into nu/nu mice with xenograft tumors were activated in vivo by HIFU 24 hours after administration. In this xenograft model, applied HIFU resulted in a 13.6 ± 6.1 mm3 bubble cloud with the IV injected particles and no bubble cloud without particles. Conclusions Iron-silica nanoshells can reduce the power and time to perform HIFU ablative therapy and can be monitored by ultrasound during low duty cycle operation.

Synthesis and surface functionalization of silica nanoparticles for nanomedicine

“…An alternative approach to HIFU therapy is in the use of high power and low duty cycle HIFU such that mechanical damage is done to the tissue with minimal thermal deposition. Perfluoropentane filled iron-silica nanoshells have been shown to be useful for mechanical ablation, which can reduce both the time and the power of the applied of ultrasound [106]. In this study 800 µg (~40 mg/kg) of nanoshells were administered intravenously into Py8119 tumor bearing mice; after 24 h HIFU was applied for 1 min at 3.5 MPa and 1.1 MHz.…”

“… In vivo HIFU of PFP filled iron silica nanoshells in Py8119 tumors in nu/nu mice: (A) B-mode imagine before HIFU [106]. (B) Bubble cavitation is observed in the focal zone of the HIFU.…”

Thermometry and ablation monitoring with ultrasound

“…Li et al more recently described the combination of color, pulse-inversion, and decorrelation Doppler to detect pulsed HIFU-induced cavitation bubbles with short transient times (36). Color Doppler has also be used to detect hollow silica nanoshells delivered to a tumor to enhance the HIFU therapy (37). …”

Phospholipid Capped Mesoporous Nanoparticles for Targeted High Intensity Focused Ultrasound Ablation

“…[9, 10] While HIFU has been used for ablation of various solid tumors [3, 11–13] including breast, prostate, kidney, liver, bone, and pancreas, the therapeutic outcomes of current HIFU methods are still unsatisfactory due to the difficulties in obtaining the required high acoustic doses, especially for deep and hypervascularized tumors. [14, 15] Thus, recurrence after HIFU treatment is often observed for such tumors because of incomplete ablation. [10, 16] In addition, intense HIFU doses can damage the healthy tissue and cause off-target effects such as skin burns and nerve injury.…”