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Cetuximab-conjugated perfluorohexane/gold nanoparticles for low intensity focused ultrasound diagnosis ablation of thyroid cancer treatment.

ABSTRACT: We report the formulation of nanoassemblies (NAs) comprising C225 conjugates Au-PFH-NAs (C-Au-PFH-NAs) for low-intensity focused ultrasound diagnosis ablation of thyroid cancer. C-Au-PFH-NAs showed excellent stability in water, phosphate-buffered saline (PBS), and 20% rat serum. Transmission electron microscopy (TEM) images also revealed the effective construction of C-Au-PFH-NAs as common spherical assemblies. The incubation of C625 thyroid carcinoma with C-Au-PFH-NAs triggers apoptosis, as confirmed by flow cytometry analysis. The C-Au-PFH-NAs exhibited antitumour efficacy in human thyroid carcinoma xenografts, where histopathological results further confirmed these outcomes. Furthermore, we were able to use low-intensity focused ultrasound diagnosis imaging (LIFUS) to examine the efficiency of C-Au-PFH-NAs in thyroid carcinoma in vivo. These findings clearly show that the use of LIFUS agents with high-performance imaging in different therapeutic settings will have extensive potential for future biomedical applications.

SUBMITTER: Liu Y

PROVIDER: S-EPMC7850351 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Phospholipid Capped Mesoporous Nanoparticles for Targeted High Intensity Focused Ultrasound Ablation.

Project description:The mechanical effects of cavitation can be effective for therapy but difficult to control, thus potentially leading to off-target side effects in patients. While administration of ultrasound active agents such as fluorocarbon microbubbles and nanodroplets can locally enhance the effects of high intensity focused ultrasound (HIFU), it has been challenging to prepare ultrasound active agents that are small and stable enough to accumulate in tumors and internalize into cancer cells. Here, this paper reports the synthesis of 100 nm nanoparticle ultrasound agents based on phospholipid-coated, mesoporous, hydrophobically functionalized silica nanoparticles that can internalize into cancer cells and remain acoustically active. The ultrasound agents produce bubbles when subjected to short HIFU pulses (?6 µs) with peak negative pressure as low as ?7 MPa and at particle concentrations down to 12.5 µg mL-1 (7 × 109 particles mL-1 ). Importantly, ultrasound agents are effectively uptaken by cancer cells without cytotoxic effects, but HIFU insonation causes destruction of the cells by the acoustically generated bubbles, as demonstrated by (2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) and lactate dehydrogenase assays and flow cytometry. Finally, it is showed that the HIFU dose required to effectively eliminate cancer cells in the presence of ultrasound agents causes only a small temperature increase of ?3.5 °C.

| S-EPMC5627974 | biostudies-literature

The efficacy and safety of high-intensity focused ultrasound ablation of benign thyroid nodules.

Project description:High-intensity focused ultrasound (HIFU) is a promising form of thermal ablation of benign thyroid nodules, but evidence supporting its use is scarce. The present review evaluated the efficacy and safety of single-session HIFU treatment of benign thyroid nodules. As reported in the literature, the extent of nodule shrinkage following treatment ranged from 48.8% to 68.8%. Like other forms of ablation, the shrinkage rate was greatest in the first 3-6 months, and the best responders were patients with small (?10 mL) nodules. Complications were uncommon, but temporary vocal cord palsy occurred in 3%-4% of patients, and was related to the distance between the HIFU beam and the recurrent laryngeal nerve. Despite being safe and efficacious, a larger-scale prospective trial is required.

| S-EPMC5885474 | biostudies-literature

The current state and future perspectives of high intensity focused ultrasound (HIFU) ablation for benign thyroid nodules.

Project description:High intensity focused ultrasound (HIFU) is a new thermoablation technique used to treat benign thyroid nodules. In this method, the ultrasound beam passes through the patient's skin and focuses very precisely on the target lesion at a distance far from the source of ultrasound generation, making HIFU the only truly non-invasive method of thermoablation developed to date. HIFU is therefore an attractive alternative to surgery and other thermoablative techniques. This review describes the principles of HIFU treatment, the selection of patients suitable for HIFU, the course and effects of treatment, and future perspectives.

| S-EPMC7044088 | biostudies-literature

Magnetic resonance-guided interstitial high-intensity focused ultrasound for brain tumor ablation.

Project description:Currently, treatment of brain tumors is limited to resection, chemotherapy, and radiotherapy. Thermal ablation has been recently explored. High-intensity focused ultrasound (HIFU) is being explored as an alternative. Specifically, the authors propose delivering HIFU internally to the tumor with an MRI-guided robotic assistant (MRgRA). The advantage of the authors' interstitial device over external MRI-guided HIFU (MRgHIFU) is that it allows for conformal, precise ablation and concurrent tissue sampling. The authors describe their workflow for MRgRA HIFU delivery.

| S-EPMC5907801 | biostudies-literature

Alterations in vaginal microbiota in uterine fibroids patients with ultrasound-guided high-intensity focused ultrasound ablation.

Project description:IntroductionVaginal microbiota dysbiosis is closely related to diseases of the vagina and uterus. Uterine fibroids (UF) are the most common benign neoplasms of the uterus, and increased diversity in vaginal microbial of UF patients. High-intensity focused ultrasound (HIFU) is effective invasive treatment for fibroids in women who are not good surgical candidates. Whether HIFU of uterine fibroids will cause the change in vaginal microbiota has not been reported. We aimed to investigate the vaginal microbiota of UF patients with/without HIFU treatment using 16S rRNA gene sequencing.MethodsVaginal secretions were collected from 77 UF patients (pre-operative and post-operative) and were used for comparative composition, diversity, and richness analyses of microbial communities.ResultsThe microbial α-diversity was significantly lower in the vaginal of UF patients with HIFU treatment. The relative abundance of some pathogenic bacteria of UF patients with HIFU treatment were significantly decreased in the bacterial phylum and genus level. Proteobacteria were found to be significantly upregulated as a biomarker in the HIFU treatment group in our study.ConclusionThese findings might confirm the effectiveness of HIFU treatment from the point of view of microbiota.

| S-EPMC10150040 | biostudies-literature

Nanoparticle-Mediated Acoustic Cavitation Enables High Intensity Focused Ultrasound Ablation Without Tissue Heating.

Project description:While thermal ablation of various solid tumors has been demonstrated using high intensity focused ultrasound (HIFU), the therapeutic outcomes of this technique are still unsatisfactory because of common recurrence of thermally ablated cancers and treatment side effects due to the high ultrasound intensity and acoustic pressure requirements. More precise ablation of tumors can be achieved by generating cavitating bubbles in the tissue using shorter pulses with higher acoustic pressures, which induce mechanical damage rather than thermal. However, it has remained as a challenge to safely deliver the acoustic pressures required for mechanical ablation of solid tumors. Here, we report a method to achieve mechanical ablation at lower acoustic pressures by utilizing phospholipid-stabilized hydrophobic mesoporous silica nanoparticles (PL-hMSN). The PL-hMSNs act as seeds for nucleation of cavitation events and thus significantly reduce the peak negative pressures and spatial-average temporal-average HIFU intensities needed to achieve mechanical ablation. Substantial mechanical damage was observed in the red blood cell or tumor spheroid containing tissue mimicking phantoms at PL-hMSN concentrations as low as 10 μg mL-1, after only 5 s of HIFU treatment with peak negative pressures ∼11 MPa and duty cycles ∼0.01%. Even the application of HIFU (peak negative pressure of 16.8 MPa and duty cycle of 0.017%) for 1 min in the presence of PL-hMSN (200 μg mL-1) did not cause any detectable temperature increase in tissue-mimicking phantoms. In addition, the mechanical effects of cavitation promoted by PL-hMSNs were observed up to 0.5 mm from the center of the cavitation events. This method may thus also improve delivery of therapeutics or nanoparticles to tumor environments with limited macromolecular transport.

| S-EPMC6702128 | biostudies-literature

Single enzyme loaded nanoparticles for combinational ultrasound-guided focused ultrasound ablation and hypoxia-relieved chemotherapy.

Project description:Constructing nanosystems that synergistically combine therapeutic and diagnostic features is of great interest to the nanomedicine community but also remains a tremendous challenge. Methods: In this work, we report novel catalytic nanoparticles composed of the enzyme catalase, encapsulated in a polymer shell and surface decorated with pH-sensitive poly(ethylene glycol) (PEGylated nCAT). These nanoparticles were used as a promoter for ultrasound (US)-guided focused ultrasound (FUS) ablation and hypoxia alleviation for application in Doxorubicin-based chemotherapy. Results: The PEGylated nCAT produced highly effectively O2 from endogenous H2O2 to ameliorate the hypoxic and therefore poor-acoustic tumor environment. The generated O2 was utilized as 1) a contrast agent for US imaging; 2) strengthening agent for FUS ablation and 3) normoxia inducer to enhance chemotherapeutic efficacy. The PEGylated nCAT exhibited favorable enzyme activity after long-term storage, and after exposure to proteolytic conditions and elevated temperatures. The pH-responsive PEGylation contributed on the one hand to an extended in vivo circulation time over 48 h and on the other hand enabled PEG cleavage in the vicinity of cancer cells to facilitate cellular uptake. Conclusion: The developed PEGylated nCAT can therefore effectively combine US-guided FUS and chemotherapy and can be regarded as a highly promising theranostic platform.

| S-EPMC6857069 | biostudies-literature

Vaginal Pessary for Uterine Repositioning during High-Intensity Focused Ultrasound Ablation of Uterine Leiomyomas.

Project description:In order to ensure safe magnetic resonance-guided, high-intensity focused, ultrasound ablation of uterine leiomyomas, the ultrasound beam path should be free of intervening scar and bowel. Pre-treatment MRI of a 9-cm long and 7.7-cm wide leiomyomatous uterus in a 39-year-old woman with menorrhagia and abdominopelvic pain initially demonstrated a focused ultrasound treatment path without a bowel between the uterus and the abdominal wall. On the day of ablation, however, multiple loops of bowel were observed in the ultrasound beam path by MRI. Uterine repositioning was accomplished with a 76-mm donut vaginal pessary, which anteverted the fundus and successfully displaced the bowel. A vaginal pessary may aid in repositioning an axial or retroverted uterus to enable ablation of uterine leiomyomas.

| S-EPMC4864147 | biostudies-literature

High-Intensity Focused Ultrasound Ablation of Uterine Fibroids - Potential Impact on Fertility and Pregnancy Outcome.

Project description:Laparoscopic myomectomy is regarded as the gold standard for women with symptomatic fibroids who wish to become pregnant. High-intensity focused ultrasound (HIFU or MRgFUS) ablation of uterine fibroids is also being discussed as a non-surgical, minimally invasive, therapeutic option. This review examines the available data on the impact of HIFU/MRgFUS on fertility and pregnancy, focusing particularly on potential direct side-effects of this type of intervention on ovaries, fallopian tubes and uterus and potential late effects on pregnancy and birth, based on the current literature. All pregnancies after HIFU/MRgFUS published to date (around 100 cases) were evaluated. The published case series suggest that HIFU/MRgFUS ablation has no impact on the rate of miscarriages or other obstetrical outcome parameters. Because no prospective studies exist which permit firm conclusions to be drawn on the impact of HIFU/MRgFUS on fertility and pregnancy outcome in women with symptomatic fibroids, this approach is currently only recommended for women with suspected fertility problems due to uterine fibroids who either decline surgery or who have an unacceptably high surgical risk.

| S-EPMC3973937 | biostudies-literature

Volumetric feedback ablation of uterine fibroids using magnetic resonance-guided high intensity focused ultrasound therapy.

Project description:ObjectiveThe purpose of this prospective multicenter study was to assess the safety and technical feasibility of volumetric Magnetic Resonance-guided High Intensity Focused Ultrasound (MR-HIFU) ablation for treatment of patients with symptomatic uterine fibroids.MethodsThirty-three patients with 36 fibroids were treated with volumetric MR-HIFU ablation. Treatment capability and technical feasibility were assessed by comparison of the Non-Perfused Volumes (NPVs) with MR thermal dose predicted treatment volumes. Safety was determined by evaluation of complications or adverse events and unintended lesions. Secondary endpoints were pain and discomfort scores, recovery time and length of hospital stay.ResultsThe mean NPV calculated as a percentage of the total fibroid volume was 21.7%. Correlation between the predicted treatment volumes and NPVs was found to be very strong, with a correlation coefficient r of 0.87. All patients tolerated the treatment well and were treated on an outpatient basis. No serious adverse events were reported and recovery time to normal activities was 2.3 ± 1.8 days.ConclusionThis prospective multicenter study proved that volumetric MR-HIFU is safe and technically feasible for the treatment of symptomatic uterine fibroids.Key points• Magnetic-resonance-guided high intensity focused ultrasound allows non-invasive treatment of uterine fibroids. • Volumetric feedback ablation is a novel technology that allows larger treatment volumes • MR-guided ultrasound ablation of uterine fibroids appears safe using volumetric feedback.

| S-EPMC3249029 | biostudies-literature

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