Publications

Prostate cancer remains one of the leading causes of cancer-related mortality. Although there were advances in cancer therapy, there is a need for advanced drug delivery strategies to improve the spatiotemporal control of therapeutic action. Here, we developed conductive, redox-responsive hybrid sponges based on glutathione-extended waterborne polyurethane (WPU-GSSG) and the electroactive polymer poly(3,4-ethylenedioxythiophene) (PEDOT) for dual-stimuli-triggered release of anticancer peptide in locoregional tumor therapy. WPU/PEDOT porous scaffolds presented lightweight and mechanically resilient structures with homogeneous loading of the pentapeptide Cys-Arg-N-methyl-Glu-Lys-Ala (CR(NMe)EKA). PEDOT incorporation significantly enhanced the electrochemical properties of the sponges, providing reversible redox activity, reduced impedance, and near-ideal capacitive behavior. The sponges supported cell adhesion and high cell viability within the three-dimensional architecture. In vitro release studies demonstrated that peptide delivery is regulated by a synergistic combination of redox and electrical stimuli. A mimetic tumor microenvironment accelerated peptide release relative to physiological conditions. Electrostimulation (+0.5 V chronoamperometry) further enhanced release kinetics, and the combined application of redox and electrical triggers enabled peptide release of up to similar to 94%, demonstrating tunable stimulus-responsive delivery. Functional assays on cancer cells supported the therapeutic potential of this platform. While WPU alone was fully cytocompatible and PEDOT-containing sponges exhibited moderate electrostimulation-dependent effects, CR(NMe)EKA-loaded conductive sponges induced a pronounced reduction in cancer cell viability under electrostimulation, decreasing survival to similar to 20%. Although further in vivo validation is required, these findings highlight the potential of multifunctional WPU/PEDOT sponges for localized, stimuli-responsive peptide delivery.

JTD Keywords: Cancer, Cell-line, Citrate transport, Design, Electrostimulation, Locoregional drugdelivery, Nanoparticle, Pedot, Ph, Polyurethane, Porosity, Prostate cancer, Redox, Scaffolds

Although we have learned much about how the brain fuels its functions over the last decades, there remains much still to discover in an organ that is so complex. This article lays out major gaps in our knowledge of interrelationships between brain metabolism and brain function, including biochemical, cellular, and subcellular aspects of functional metabolism and its imaging in adult brain, as well as during development, aging, and disease. The focus is on unknowns in metabolism of major brain substrates and associated transporters, the roles of insulin and of lipid droplets, the emerging role of metabolism in microglia, mysteries about the major brain cofactor and signaling molecule NAD+, as well as unsolved problems underlying brain metabolism in pathologies such as traumatic brain injury, epilepsy, and metabolic downregulation during hibernation. It describes our current level of understanding of these facets of brain energy metabolism as well as a roadmap for future research. This article details current knowledge and major unknowns in brain energy metabolism and lays out a roadmap for future research.image

JTD Keywords: Acetate, Acetyl-coa, Aerobic glycolysis, Atp-citrate lyase, Extracellular glutamate concentration, Fatty-acid transport, Glucose-metabolism, Glut4, In-vivo, Insulin, Lipid droplet accumulation, Nicotinamide adenine-dinucleotide, Noradrenaline, Obese zucker rats, Rat cerebral-cortex

Alzheimer's disease is characterized by a combination of several neuropathological hallmarks, such as extracellular aggregates of beta amyloid (Aβ). Numerous alternatives have been studied for inhibiting Aβ aggregation but, at this time, there are no effective treatments available. Here, we developed the tri-component nanohybrid system AuNPs@POM@PEG based on gold nanoparticles (AuNPs) covered with polyoxometalates (POMs) and polyethylene glycol (PEG). In this work, AuNPs@POM@PEG demonstrated the inhibition of the formation of amyloid fibrils, showing a 75% decrease in Aβ aggregation in vitro. As it is a potential candidate for the treatment of Alzheimer's disease, we evaluated the cytotoxicity of AuNPs@POM@PEG and its ability to cross the blood-brain barrier (BBB). We achieved a stable nanosystem that is non-cytotoxic below 2.5 nM to human neurovascular cells. The brain permeability of AuNPs@POM@PEG was analyzed in an in vitro microphysiological model of the BBB (BBB-on-a-chip), containing 3D human neurovascular cell co-cultures and microfluidics. The results show that AuNPs@POM@PEG was able to cross the brain endothelial barrier in the chip and demonstrated that POM does not affect the barrier integrity, giving the green light to further studies into this system as a nanotherapeutic.

JTD Keywords: beta-amyloid, blood-brain barrier organ-on-a-chip, cellular uptake, citrate, cytotoxicity, electrocatalytic reduction, gold nanoparticles, hypothesis, nanorods, polyoxometalates, size, stability, surface, Alzheimers-disease, Blood–brain barrier organ-on-a-chip, Gold nanoparticles, Nanovehicle, Polyoxometalates, Β-amyloid