Transcranial application of magnetic pulses for improving brain drug delivery efficiency via intranasal injection of magnetic nanoparticles.

As the blood-brain barrier (BBB) hinders efficient drug delivery to the brain, drug delivery via the intranasal pathway, bypassing the BBB, has received considerable attention. However, intranasal administration still has anatomical and physiological limitations, necessitating further solutions to enhance effectiveness. In this study, we used transcranial magnetic stimulation (TMS) on fluorescent magnetic nanoparticles (MNPs) of different sizes (50, 100, and 300 nm) to facilitate MNP's transportation and delivery to the brain parenchyma. To validate this concept, anesthetized rats were intranasally injected with the MNPs, and TMS was applied to the center of the head. As the result, a two-fold increase in brain MNP delivery was achieved using TMS compared with passive intranasal administration. In addition, histological analysis that was performed to investigate the safety revealed no gross or microscopic damages to major organs caused by the nanoparticles. While future studies should establish the delivery conditions in humans, we expect an easy clinical translation in terms of device safety, similar to the use of conventional TMS. The strategy reported herein is the first critical step towards effective drug transportation to the brain.

[Corrigendum] Effect of duty cycles of tumor­treating fields on glioblastoma cells and normal brain organoids.

Subsequently to the publication of the above article, the authors have realized that Fig. 3 on p. 6, showing the results of bioluminescence imaging of U87 and U373 cells after applying tumor­treating fields for 72 h, was published containing an erroneous image. Essentially, the data analysis panel for the U87 / U87TTF experiment was inadvertently copied across for the U373 / U373TTF experiment for the '75% Duty' experimental condition. The revised version of Fig. 3, now showing the correct data analysis panel for the '75% Duty' U373 / U373TTF experiment, is shown below. The authors confirm that the error made in the presentation of Fig. 3 did not adversely affect the conclusions reported in this paper, and they are grateful to the Editor of International Journal of Oncology for granting them this opportunity to publish a Corrigendum. All the authors agree to the publication of this Corrigendum; they also apologize to the readership for any inconvenience caused. [International Journal of Oncology 60: 8, 2022; DOI: 10.3892/ijo.2021.5298].

Effect of duty cycles of tumor­treating fields on glioblastoma cells and normal brain organoids.

Tumor­treating fields (TTFields) are emerging cancer therapies based on alternating low­intensity electric fields that interfere with dividing cells and induce cancer cell apoptosis. However, to date, there is limited knowledge of their effects on normal cells, as well as the effects of different duty cycles on outcomes. The present study evaluated the effects of TTFields with different duty cycles on glioma spheroid cells and normal brain organoids. A customized TTFields system was developed to perform in vitro experiments with varying duty cycles. Three duty cycles were applied to three types of glioma spheroid cells and brain organoids. The efficacy and safety of the TTFields were evaluated by analyzing the cell cycle of glioma cells, and markers of neural stem cells (NSCs) and astrocytes in brain organoids. The application of the TTFields at the 75 and 100% duty cycle markedly inhibited the proliferation of the U87 and U373 compared with the control. FACS analysis revealed that the higher the duty cycle of the applied fields, the greater the increase in apoptosis detected. Exposure to a higher duty cycle resulted in a greater decrease in NSC markers and a greater increase in glial fibrillary acidic protein expression in normal brain organoids. These results suggest that TTFields at the 75 and 100% duty cycle induced cancer cell death, and that the neurotoxicity of the TTFields at 75% was less prominent than that at 100%. Although clinical studies with endpoints related to safety and efficacy need to be performed before this strategy may be adopted clinically, the findings of the present study provide meaningful evidence for the further advancement of TTFields in the treatment of various types of cancer.

Developing a Computational Model of Renal Nerves and Surgical System for Laparoscopic Renal Denervation.

The sympathetic nervous system was known to play an important role in resistant hypertension. Surgical sympathectomy for renal sympathetic nerve removal were performed since the 1930s. Although effective, it had many serious side effects and complications due to non-selective property. Recently, catheter based RDN system using radiofrequency (RF) ablation was developed and considered promising, however, it failed in sham controlled trial. Therefore, there are needs for safe and effective RDN strategies considering the anatomical structure of the renal arteries and sympathetic nerves. In this paper, we propose a novel surgical instruments for laparoscopic renal denervation (RDN) to treat of resistant hypertension through a 3D realistic model using nephrectomy tissues. Laparoscopic RDN is a new surgical approach to remove renal sympathetic nerves.

Design and simulation of novel laparoscopic renal denervation system: a feasibility study.

PURPOSE: In this study, we propose a novel laparoscopy-based renal denervation (RDN) system for treating patients with resistant hypertension. In this feasibility study, we investigated whether our proposed surgical instrument can ablate renal nerves from outside of the renal artery safely and effectively and can overcome the depth-related limitations of the previous catheter-based system with less damage to the arterial walls. METHOD: We designed a looped bipolar electrosurgical instrument to be used with laparoscopy-based RDN system. The tip of instrument wraps around the renal artery and delivers the radio-frequency (RF) energy. We evaluated the thermal distribution via simulation study on a numerical model designed using histological data and validated the results by the in vitro study. Finally, to show the effectiveness of this system, we compared the performance of our system with that of catheter-based RDN system through simulations. RESULTS: Simulation results were within the 95% confidence intervals of the in vitro experimental results. The validated results demonstrated that the proposed laparoscopy-based RDN system produces an effective thermal distribution for the removal of renal sympathetic nerves without damaging the arterial wall and addresses the depth limitation of catheter-based RDN system. CONCLUSIONS: We developed a novel laparoscope-based electrosurgical RDN method for hypertension treatment. The feasibility of our system was confirmed through a simulation study as well as in vitro experiments. Our proposed method could be an effective treatment for resistant hypertension as well as central nervous system diseases.