Directed enzyme prodrug therapy (DEPT) involves the delivery of a prodrug-activating enzyme to a solid tumour site, followed by the subsequent activation of an administered prodrug. One of the most studied enzyme–prodrug combinations is the nitroreductase from Escherichia coli (NfnB) with the prodrug CB1954 [5-(aziridin-1-yl)-2,4-dinitro-benzamide]. One of the major issues faced by DEPT is the ability to successfully internalize the enzyme into the target cells. NfnB has previously been genetically modified to contain cysteine residues (NfnB-Cys) which bind to gold nanoparticles for a novel DEPT therapy called magnetic nanoparticle directed enzyme prodrug therapy (MNDEPT). One cellular internalisation method is the use of cell-penetrating peptides (CPPs), which aid cellular internalization of cargo. Here the cell-penetrating peptides: HR9 and Pep-1 were tested for their ability to conjugate with NfnB-Cys. The conjugates were further tested for their potential use in MNDEPT, as well as conjugating with the delivery vector intended for use in MNDEPT and tested for the vectors capability to penetrate into cells.
Attention Deficit/Hyperactivity Disorder (ADHD) is one of the most frequent psychiatric disorders at school age. The core symptoms of hyperactivity, impulsivity and inattention emerge before the age of seven and are associated with severe impairment of the child's everyday functioning (family, school, leisure time). Seventy percent of the affected children show at least one comorbid psychiatric condition or learning disorder/academic impairment. ADHD is one of the most widely investigated disorders in child and adolescent psychiatry. A multitude of imaging (fMRI) and genetic studies comparing children with ADHD and typically developing children have provided clear evidence for the neurobiological foundation of ADHD. Nevertheless, environmental, familial and academic factors play an important role with regard to the persistence and severity of the disorder. Treatment should be preferentially multimodal, with interventions targeting the child, the parents, and, if possible, the teacher. Society with its specific requirements and constraints, and also school, are not well adjusted for children that are different, hyperactive and easily distracted. However, many of these children also have resources. When fascinated by a task, they may show persistence and commitment.
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