Heat generation of aqueously dispersed CoFe2O4 nanoparticles as heating agents for magnetically activated drug delivery and hyperthermia

Self-heating from magnetic nanoparticles under AC magnetic field can be used either for hyperthermia or to trigger the release of an anti-cancer drug, using thermo-responsive polymers. The heat generated by applying an AC magnetic field depends on the properties of magnetic nanoparticles (composition, size, crystal structure) as well as the frequency and amplitude of the magnetic field. Before these systems can be efficiently applied for in vitro or in vivo studies, a thorough analysis of the magnetically induced heating is required. In this study, CoFe₂O₄ nanoparticles were synthesized, dispersed in water, and investigated as heating agents for magnetic thermo-drug delivery and hyperthermia. The temperature profiles and infrared (IR) camera images of heat generation of CoFe₂O₄ nanoparticles under various AC magnetic fields of 127–700 Oe at 195, 231, and 266 kHz were measured using an IR thermacam, excluding the external AC magnetic field interruption. The CoFe₂O₄ nanoparticles were successfully dispersed in water using an 11-mercaptoundecanoic acid ligand exchange method to exchange the solvent used for synthesis of hexane for water. During the heating experiments, each of CoFe₂O₄ nanoparticle solutions reached a steady state where the temperature rose between 0.1 and 42.9 °C above ambient conditions when a magnetic field of 127–634 Oe was applied at 231 or 266 kHz. The heat generation was found to be dependent on the intensity of AC magnetic field and applied frequency. Therefore, the desired heating for magnetically triggered drug delivery or hyperthermia could be achieved in water-dispersed CoFe₂O₄ nanoparticles by adjusting the AC magnetic field and frequency.     

Using ultrasound CBE imaging without echo shift compensation for temperature estimation

Clinical trials have demonstrated that hyperthermia improves cancer treatments. Previous studies developed ultrasound temperature imaging methods, based on the changes in backscattered energy (CBE), to monitor temperature variations during hyperthermia. Echo shift, induced by increasing temperature, contaminates the CBE image, and its tracking and compensation should normally ensure that estimations of CBE at each pixel are correct. To obtain a simplified algorithm that would allow real-time computation of CBE images, this study evaluated the usefulness of CBE imaging without echo shift compensation in detecting distributions in temperature. Experiments on phantoms, using different scatterer concentrations, and porcine livers were conducted to acquire raw backscattered data at temperatures ranging from 37 °C to 45 °C. Tissue samples of pork tenderloin were ablated in vitro by microwave irradiation to evaluate the feasibility of using the CBE image without compensation to monitor tissue ablation. CBE image construction was based on a ratio map obtained from the envelope image divided by the reference envelope image at 37 °C. The experimental results demonstrated that the CBE image obtained without echo shift compensation has the ability to estimate temperature variations induced during uniform heating or tissue ablation. The magnitude of the CBE as a function of temperature obtained without compensation is stronger than that with compensation, implying that the CBE image without compensation has a better sensitivity to detect temperature. These findings suggest that echo shift tracking and compensation may be unnecessary in practice, thus simplifying the algorithm required to implement real-time CBE imaging.     

Heart ablation using a planar rectangular high intensity ultrasound transducer and MRI guidance

The aim of this study was to evaluate a flat rectangular (3 × 10 mm²) MRI compatible transducer operating at 5 MHz. The main task was to explore the feasibility of creating deep lesions in heart at a depth of at least 15 mm. The size of thermal necrosis in heart tissue was estimated as a function of power and time using a simulation model. The system was then tested in an excised lamb heart. In this study, we were able to create lesions of 15 mm deep with acoustic power of 6 W for an exposure of approximately 1 min. The contrast to noise ratio (CNR) between lesion and heart tissue was evaluated using fast spin echo (FSE). The CNR value was approximately 22 using T1 W FSE. Maximum CNR was achieved with repetition time (TR) between 300 and 800 ms. Using T2W FSE, the corresponding CNR was approximately 13 for the 14 in vivo experiments. The average lesion depth was 11.93 mm with a standard deviation of 0.62 mm. In vivo irradiation conditions were 6 W for 60 s. The size of the lesion in the other two dimensions was close to 3 × 10 mm² (size of the transducer element).     

PEO coated magnetic nanoparticles for biomedical application

This paper reports on the preparation, characterization and stealthiness of superparamagnetic nanoparticles (magnetite Fe₃O₄) with a 5 nm diameter and stabilized in water (pH ? 6.5) by a shell of water-soluble poly(ethylene oxide) (PEO) chains. Two types of diblock copolymers, i.e., poly(acrylic acid)-b-poly(ethylene oxide), PAA-PEO, and poly(acrylic acid)-b-poly(acrylate methoxy poly(ethyleneoxide)), PAA-PAMPEO, were prepared as stabilizers with different compositions and molecular weights. At pH ? 6.5, the negatively ionized PAA block interacts strongly with the positively-charged nanoparticles, thus playing the role of an anchoring block. Aggregates of coated nanoparticles were actually observed by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The hydrodynamic diameter was in the 50-100 nm range and the aggregation number (number of nanoparticles per aggregate) was lying between several tens and hundred. Moreover, the stealthiness of these aggregates was assessed “in vitro” by the hemolytic CH50 test. No response of the complement system was observed, such that biomedical applications can be envisioned for these magnetic nanoparticles. Preliminary experiments of magnetic heating (10 kA/m; 108 kHz) were performed and specific absorption rate varied from 2 to 13 W/g_(Fe).     

热疗用聚焦脉冲声场的时域和频域特性研究

本文用传递函数的概念导出了凹球面聚焦脉冲声扬的简洁表达式,从数值计算上和实验上研究了这种声场和中轴线上不同位置处声压信号的持续时间和频谱特征,分析了它们对热疗的影响。     

环形相控阵热疗系统照射下肝区的吸收功率分布

本文用数值方法研究了在环形相控阵热疗系统照射下肝区的吸收功率的分布。以肝区CT图为模型,推算了病例的积沉功率分布图形。结果表明,调节阵列的相位和幅度,该系统可以在肝区得到有效的热疗分布。     

无种子法纳米金棒的制备及其对肿瘤细胞光热治疗效应研究

采用简便快捷的无种子法一步完成了纳米金棒的制备.通过改变实验条件可以调控纳米金棒的吸收峰从可见到近红外转移.将巯基聚乙二醇(PEG-SH)置换金棒表面的十六烷基三甲基溴化铵(CTAB)分子,大大提高了金棒的生物相容性.制备的纳米金棒在近红外(NIR)光照射下对肿瘤细胞有很好的杀伤效果.研究结果为纳米金棒用于抗肿瘤治疗提供了实验基础.     

Magnetic particle hyperthermia—biophysical limitations of a visionary tumour therapy

Loss processes being relevant for magnetic particle hyperthermia are analysed with respect to specific loss power under the condition of a limitation of the alternating magnetic field amplitude and frequency. Extrapolations to the maximum specific loss power of magnetic nanoparticles are discussed and conclusions are drawn with respect to the minimum particle concentration being necessary for hyperthermia or thermoablation under intra-tumoural or systemic particle supply. As a result, much efforts are necessary to render magnetic particle hyperthermia a valuable tumour therapy keeping at least part of the promises found in literature.     

Ferrite-enhanced MRI monitoring in hyperthermia

In an MRI hyperthermia hybrid system, T₁ changes are investigated for monitoring thermal therapy at 0.2 T. The water bolus, which is needed for power transmission and cooling of the skin, limits MR image quality by signal compression and artifacts. Superparamagnetic ferrofluid in different concentration was investigated with MR relaxometry and MRI methods. We found that using ferrofluid in a low concentration of 70–90 ppm magnetite the water signal can be suppressed without susceptibility artifacts. With our method of signal suppression, a significant improvement of spatial and temporal resolution is possible. The ferrofluid is stable and allows RF heating at 100 MHz. This method of signal extinction may also be useful for other experimental setups where suppression of water is necessary.     

Newer nanoparticles in hyperthermia treatment and thermometry

Abstract  Heating tumors by nanoparticles and resistance in hypoxic tumor cells to a high temperature is emerging as an effective tool in therapeutic oncology as nanomedicine tool. The art of imaging temperature in a tumor at various locations is emerging as the selective approach of hyperthermia to monitor temperature and treat the tumor. However, thermometry and tumor cell interaction with nanoparticles may monitor and evaluate the tumor cell survival after exposure to high physiological temperatures. The application of 10–100 nanometer sized nanoparticles in tumor hyperthermia has emerged as an effective monitoring tool as magnetic resonance (MR) thermal mapping. The temperature and nanoparticle magnetic moment relationship is specific. Furthermore, there are two main issues that are unsolved as of yet. First issue is the relationship of tumor energy changes due to tumor magnetization; linear attenuation after magnetic field and X-ray exposure with tissue temperature increase. The second issue is the undefined behavior of the nanoparticle inside the tumor as diamagnetic or paramagnetic can be therapeutic and it depends on the tumor tissue temperature. In vivo imaging such as MR thermometry mapping of different hypoxic tumor locations solves these issues to some extent. The art of the nanoparticle-induced hyperthermia does have a great impact on public health as alternative therapeutic oncology. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.