The novel design of an intelligent anti-depression transdermal drug delivery system.

Depression is a type of mental disorder with a significant and persistent low mood as the main clinical feature. It is often accompanied by symptoms such as slow thinking, decreased will, loss of appetite, and weight loss. The current treatment methods for depression are mainly medical treatment, psychotherapy, and physical therapy. These treatments are dependent on the patient's autonomy and the patients may suspend treatment due to forgetting or refusing. Therefore, an anti-depressant intelligent drug release system was designed, which can achieve autonomously controlled doses for the treatment of depression by transdermal drug delivery system. The work of this study is as follows: (1) The first module: the electrothermal material heating layer. Several preparation methods were screened, and multiple sets of graphene (GE) electric thermogenic layers were successfully prepared. After increasing the actual energization area to 1 cm × 1 cm, the GE electric thermogenic layer is used as the heating layer of the electrothermal material of the system, and can reach a uniform surface temperature of (45 ± 0.5) °C within 15 s at a voltage of 6 V keeping the temperature fluctuation range not exceeding ±0.03 °C, and the resistance fluctuation range not exceeding ±20 Ω, which plays a role in controlling the temperature and heat treatment of the drug loaded gel layer. (2) The second module: the drug-loaded gel layer. Based on the L16 (45) orthogonal test, the best formulation and process of N-Isopropyl acrylamide-Acrylamide copolymer (P(NIPAAm-co-AAm)) hydrogel was determined. Then, the percutaneous permeability of Selegiline liposome was studied in vitro. (3) A rat model of depression was established using chronic unpredictable mild stress (CUMS) combined with separation. From the aspects of behavior (body weight, sucrose preference test, forced swimming test, open field test) and biochemical indexes (serum proinflammatory cytokines (IL-1ß, TNF-α), hippocampus HE staining observation), the therapeutic effect of hyperthermia, Selegiline oral administration and transdermal administration was discussed.

Fine-tuned magnetic nanobubbles for magnetic hyperthermia treatment of glioma cells.

Magnetic nanoparticle (MNP) induced magnetic hyperthermia has been demonstrated as a promising technique for the treatment of brain tumor. However, lower heating efficiency resulting from low intratumoral accumulation of magnetic nanomaterials is still one of the significant limitations for their thermotherapeutic efficacy. In this study, we have designed a nanobubble structure with MNPs decorated on the shell, which leads to the improvement of magnetocaloric performance under an alternating magnetic field. First, the phospholipid coupled with MNPs as the shell to be self-assembled magnetic nanobubbles (MNBs) was fabricated by a temperature-regulated repeated compression self-assembly approach. Then, the optimal magnetic heating concentration, electric current parameters for producing the magnetic field, and the number of magnetic heating times were investigated for tuning the better magnetoenergy conversion. Finally, the well-defined geometrical orientation of MNPs on the nanobubble structure enhanced hypothermia effect was investigated. The results demonstrate that the MNBs could promote the endocytosis of magnetic nanoparticles by glioma cells, resulting in better therapeutic effect. Therefore, the controlled assembly of MNPs into well-defined bubble structures could serve as a new hyperthermia agent for tumor therapy.

Some Preliminary Results to Eradicate Leukemic Cells in Extracorporeal Circulation by Actuating Doxorubicin-Loaded Nanochains of Fe3O4 Nanoparticles.

Leukemia is a non-solid cancer which features the malignant proliferation of leukocytes. Excessive leukocytes of lesions in peripheral blood will infiltrate organs, resulting in intumescence and weakening treatment efficiency. In this study, we proposed a novel approach for targeted clearance of the leukocytes in the peripheral blood ex vivo, which employed magnetic nanochains to selectively destroy the leukocytes of the lesions. The nanochains were doxorubicin-loaded nanochains of Fe3O4 nanoparticles which were fabricated by the solvent exchange method combined with magnetic field-directed self-assembly. Firstly, the nanochains were added into the peripheral blood during extracorporeal circulation and subjected to a rotational magnetic field for actuation. The leukocytes of the lesion were then conjugated by the nanochains via folic acid (FA) targeting. Finally, the rotational magnetic field actuated the nanochains to release the drugs and effectively damage the cytomembrane of the leukocytes. This strategy was conceptually shown in vitro (K562 cell line) and the method's safety was evaluated in a rat model. The preliminary results demonstrate that the nanochains are biocompatible and suitable as drug carriers, showing direct lethal action to the leukemic cells combined with a rotational magnetic field. More importantly to note is that the nanochains can be effectively kept from entry into the body. We believe this extracorporeal circulation-based strategy by activating nanochains magnetically could serve as a potential method for leukemia treatment in the future.

Optical Imaging and High-Accuracy Quantification of Intracellular Iron Contents.

Precise quantification of intracellular iron contents is important to biomedical applications of magnetic nanoparticles. Current approaches for iron quantification rely on specialized instruments while most only yield iron quantities averaged over plenty of cells. Here, a simple and robust approach, combining digital optical microscopy with the Beer-Lambert's law, that allows for imaging stainable iron distribution in individual cells and the quantification of stainable iron contents with an unprecedented accuracy of femtogram per pixel, is presented. It is further shown that this approach enables studying of the internalization and reduction dynamics of super-paramagnetic iron oxide nanoparticles (SPIONs) by stem cells in single cell level.

Cell Temperature Measurement for Biometabolism Monitoring.

Temperature is an important factor in the process of life, as thermal energy transfer participates in all biological events in organisms. Due to technical limitations, there is still a lot more information to be explored regarding the correlation between life activities and temperature changes. In recent years, the emergence of a variety of new temperature measurement methods has facilitated further research in this field. Here, we introduce the latest advances in temperature sensors for biological detection and their related applications in metabolic research. Various technologies are discussed in terms of their advantages and shortcomings, and future prospects are presented.

Exploring the 'cold/hot' properties of traditional Chinese medicine by cell temperature measurement.

Context: It is common sense that chewing a mint leaf can cause a cooling feeling, while chewing ginger root will produce a burning feeling. In Traditional Chinese Medicine (TCM), this phenomenon is referred to as 'cold/hot' properties of herbs. Herein, it is reported that TCM with different "cold/hot" properties have different effects on the variation of cells.Objective: To explore the intrinsic 'cold/hot' properties of TCM from the perspective of cellular and molecular biology.Materials and methods: A375 cells were selected using Cancer Cell Line Encyclopaedia (CCLE) analysis and western blots. Hypaconitine and baicalin were selected by structural similarity analysis from 56 and 140 compounds, respectively. A wireless thermometry system was used to measure cellular temperature change induced by different compounds. Alteration of intracellular calcium influx was investigated by means of calcium imaging.Results: The IC50 values of GSK1016790A, HC067047, hypaconitine, and baicalin for A375 cells are 8.363 nM, 816.4 µM, 286.4 µM and 29.84 µM, respectively. And, 8 µM hypaconitine induced obvious calcium influx while 8 µM baicalin inhibited calcium influx induced by TRPV4 activation. Cellular temperature elevated significantly when treated with GSK1016790A or hypaconitine, while the results were reversed when cells were treated with HC067047 or baicalin.Discussion and conclusions: The changes in cellular temperature are speculated to be caused by the alteration of intracellular calcium influx mediated by TRPV4. In addition, the 'cold/hot' properties of compounds in TCM can be classified by using cellular temperature detection.

A new approach of electrochemical etching fabrication based on drop-off-delay control.

W-Pt micro-nano-thermocouple is a brand new sensor for intracellular temperature measurement. As a nanodevice, it is based on the electrochemical etching method of which the shape is directly related to the performance. Although much research has been done on how to control the shape of the tungsten tip through electrochemical etching method, preparing different shapes requires different fabrication methods. In this article, we proposed a flexible and general control method which can fit all the fabrication methods by merely modifying the software. Moreover, this method based on drop-off-delay time control is capable of controlling the duration of the electrochemical reaction during the final formation of the tungsten tip. Based on this method, the cone angle can be set to any value from 5° to 30° with the radius of curvature maintaining from 2 nm to 5 nm. Additionally, the sophisticated fabrication of W-Pt micro-nano-thermocouple was designed to be automatically completed by three workshops in batches. The efficiency and uniformity of W-Pt micro-nano-thermocouple fabrication were well improved.