ABSTRACT
Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor and known for its challenging prognosis. Sonodynamic therapy (SDT) is an innovative therapeutic approach that shows promise in tumor elimination by activating sonosensitizers with low-intensity ultrasound. In this study, a novel sonosensitizer is synthesized using Cu-doped carbon dots (Cu-CDs) for the sonodynamic treatment of GBM. Doping with copper transforms the carbon dots into a p-n type semiconductor having a bandgap of 1.58 eV, a prolonged lifespan of 10.7 µs, and an improved electron- and hole-separation efficiency. The sonodynamic effect is efficiency enhanced. Western blot analysis reveals that the Cu-CDs induces a biological response leading to cell death, termed as cuproptosis. Specifically, Cu-CDs upregulate dihydrosulfanyl transacetylase expression, thereby establishing a synergistic therapeutic effect against tumor cell death when combined with SDT. Furthermore, Cu-CDs exhibit excellent permeability through the blood-brain barrier and potent anti-tumor activity. Importantly, the Cu-CDs effectively impede the growth of glioblastoma tumors and prolong the survival of mice bearing these tumors. This study provides support for the application of carbon-based nanomaterials as sonosensitizers in tumor therapy.
ABSTRACT
A miniaturized, low-cost high-intensity focused ultrasound device is developed for the problems of cross-contamination and uneven sample fragmentation in conventional ultrasound devices. This device generates ultrasonic waves through a concave spherical self-focusing piezoelectric ceramic piece, and creates a cavitation effect in the focusing area to achieve sample fragmentation. The feasibility of the device is demonstrated by physical simulation, then a driving circuit with adjustable power is designed and manufactured to generate 0 ~ 22.4 W acoustic power, and finally paraffin-embedded sample dewaxing experiments are performed to verify the validation of the device. The experimental results show that the dewaxing efficiency and safety of the high-intensity focused ultrasound device is significantly better than those of traditional chemical methods, and this device is comparable with commercial ultrasonic instruments. In summary, the high-intensity focused ultrasound device is expected to be applied in automated nucleic acid extraction and purification equipment and has a broad application prospect in the field of sample pre-processing.
Subject(s)
Acoustics , Equipment Design , Computer SimulationABSTRACT
Formalin-fixed paraffin-embedded (FFPE) tissue samples are routinely used in prospective and retrospective studies. It is crucial to obtain high-quality nucleic acid (NA) from FFPE samples for downstream molecular analysis, such as quantitative polymerase chain reaction (PCR), Sanger sequencing, next-generation sequencing, and microarray, in both clinical diagnosis and basic research. The current NA extraction methods from FFPE samples using chemical solvent are tedious, environmentally unfriendly, and unamenable to automation or field deployment. We present a tool for NA extraction from FFPE samples using a high-intensity focused ultrasound (HIFU) technology. A cartridge strip containing reagents for FFPE sample deparaffinization and NA extraction and purification is operated by an automation tool consisting of a HIFU module, a liquid handling robot unit, and accessories including a thermal block and magnets. The HIFU module is a single concaved piezoelectric ceramic plate driven by a current-mode class-D power amplifier. Based on the ultrasonic cavitation effects, the HIFU module provides highly concentrated energy introducing paraffin emulsification and disintegration. The high quantity and quality of NA extracted using the reported system are evaluated by PCR and compared with the quantity and quality of NA extracted using the current standard methods.
