Redox-Sensitive Nanocomplex for Targeted Delivery of Melittin

Although peptide therapeutics have been explored for decades, the successful delivery of potent peptides in vitro and in vivo remains challenging due to the poor stability, low cell permeability, and off-target effects. We developed a redox sensitive polymer-based nanocomplex which can efficiently and stably deliver the peptide drug melittin for cancer therapy. The nanocomplex selectively targets cancer cells through lactobionic acid mediated endocytosis and releases melittin intracellularly upon the trigger of elevated redox potential. In vivo study proved that the targeted nanocomplex shows excellent potency in inhibiting tumor growth in a xenograft colon cancer mouse model. Thus, the polymer/melittin nanocomplexes will provide a new approach for melittin based cancer therapy

Smart Mesoporous Silica Nanoparticles for Protein Delivery

Mesoporous silica nanoparticles (MSN) have attracted a lot of attention during the past decade which is attributable to their versatile and high loading capacity, easy surface functionalization, excellent biocompatibility, and great physicochemical and thermal stability. In this review, we discuss the factors affecting the loading of protein into MSN and general strategies for targeted delivery and controlled release of proteins with MSN. Additionally, we also give an outlook for the remaining challenges in the clinical translation of protein-loaded MSNs

Redox Potential-Sensitive <i>N</i>‑Acetyl Cysteine-Prodrug Nanoparticles Inhibit the Activation of Microglia and Improve Neuronal Survival

One hallmark of neuroinflammation is the activation of microglia, which triggers the production and release of reactive oxygen species (ROS), nitrate, nitrite, and cytokines. <i>N</i>-Acetyl cysteine (NAC) is a free radical scavenger that is involved in the intracellular and extracellular detoxification of reactive oxygen species in the brain. However, the clinical application of NAC is limited by its low bioavailability and short half-life. Herein, NAC was conjugated to a polymer through a disulfide bond to form a NAC-prodrug nanoparticle (NAC-NP). Dynamic light scattering found that the NAC-NP has a size of around 50 nm. In vitro studies revealed that the release of NAC from NAC-NP is responsive to its environmental redox potential. For mimicking neuroinflammation in vitro, microglial cells were stimulated by a lipopolysaccharide (LPS), and the effect of NAC-NP on activated microglia was investigated. The study found that the morphology as well as the expression of microgliosis marker Iba-1 of the cells treated with NAC-NPs and LPS were close to those of control cells, indicating that NAC-NPs can inhibit the activation of microglia stimulated by LPS. Compared with free NAC, the production of ROS, NO₃-, NO₂-, tumor necrosis factor-α (TNF-α), and interleukin (IL)-1β from the LPS-stimulated microglia was considerably decreased when the cells were pretreated with NAC-NPs. Furthermore, LPS-induced microglial phagocytocis of neurons was inhibited in the presence of NAC-NPs. These results indicated that NAC-NPs are more effective than free NAC for reversing the effect of LPS on microglia and subsequently protecting neurons

A case of labial lentigines in Peutz-Jeghers syndrome treated using a Q-switched alexandrite laser

Peutz-Jeghers syndrome (PJS) is a polygenic autosomal dominant disease characterized by multiple gastrointestinal polyps and pigmentation of the mucosa and skin. While there are a few reports regarding successful treatment of intestinal polyps in PJS, there is little research regarding treatment of mucocutaneous melanosis. This study investigated the many advantages of using a Q-switched alexandrite laser to treat mucocutaneous melanosis. In this case, a 19-year-old male with PJS presented with labial lentigines and received two Q-switched alexandrite laser treatments in 2018. Subsequently, the efficacy of the treatment was evaluated. The result of the evaluation was that, after the two laser treatments, the labial lentigines were successfully removed, and there were no complications

Research on Heat Dissipation of Multi-Chip LED Filament Package

By studying the substrate material, structure, chip distribution, and array form of the multi-chip light-emitting diode (LED) package, the heat-dissipation capacity of the LED package is improved. Finite element analysis and steady-state thermal analysis are used to simulate and analyze LED packages with different materials and structures. Using the theory of LED illuminance and uniformity, the illuminance of some structures is computed. The results show that the change of substrate material and structure can greatly impact heat dissipation, while changing array forms has little effect on heat dissipation. By improving the spatial distribution of the chip, the temperature superposition problem of the substrate is solved, and the illuminance and uniformity are improved while dissipating heat. The LED filaments of the combined, equidistant, chip-distribution mode have improved heat dissipation. The S-type equal difference has the highest illumination and high illumination uniformity

Heat Dissipation Characteristics of IGBT Module Based on Flow-Solid Coupling

With the increase of power level and integration in electric vehicle controllers, the heat flux of the key silicon-based IGBT (Insulated Gate Bipolar Transistor) device has reached its physical limit. At present, third-generation semiconductor devices including SiC MOSFETs (Metal-Oxide-Semiconductor Field-Effect Transistor) are gradually replacing the dominant IGBT module. The hybrid IGBT module consists of both and can improve the performance and reduce the cost of controllers. Limits due to the installation space, location, and other conditions in the car make it difficult to meet the requirements of controllers with an air-cooled heatsink due to their large size and limited heat dissipation capacity. A smaller and more powerful water-cooled heatsink case is required to ensure the heat dissipation of the IGBT in the controller. Based on previous experience in finite element numerical simulation, hydrodynamics calculation, and heat transfer calculation, ANSYS Workbench finite element software was used to analyze the thermal resistance of each structure inside the module and the heatsink structure. The fluid characteristics and heat transfer performance of three different flow channel structures were analyzed, and the design of the cooling flow fin was improved to provide a reference for the heat dissipation of the hybrid IGBT module

pH and Redox Dual Responsive Nanoparticle for Nuclear Targeted Drug Delivery

To mimic the clinic dosing pattern, initially administering high loading dose and then low maintenance dose, we designed a novel poly­(2-(pyridin-2-yldisulfanyl)­ethyl acrylate) (PDS) based nanoparticle delivery system. Side chain functional PDS was synthesized by free radical polymerization. Polyethylene glycol and cyclo­(Arg-Gly-Asp-d-Phe-Cys) (cRGD) peptide was conjugated to PDS through thiol–disulfide exchange reaction to achieve RPDSG polymer. RPDSG/DOX, RPDSG nanoparticle loaded with doxorubicin, was fabricated by cosolvent dialysis method. The size of the nanoparticles was 50.13 ± 0.5 nm in PBS. The RPDSG/DOX nanoparticle is stable in physiological condition while quickly releasing doxorubicin with the trigger of acidic pH and redox potential. Furthermore, it shows a two-phase release kinetics, providing both loading dose and maintenance dose for cancer therapy. The conjugation of RGD peptide enhanced the cellular uptake and nuclear localization of the RPDSG/DOX nanoparticles. RPDSG/DOX exhibits IC₅₀ close to that of free doxorubicin for HCT-116 colon cancer cells. Due to the synergetic effect of RGD targeting effect and its two-phase release kinetics, RPDSG/DOX nanoparticles display significantly higher anticancer efficacy than that of free DOX at concentrations higher than 5 μM. These results suggest that RPDSG/DOX could be a promising nanotherapeutic for tumor-targeted chemotherapy