Systemic Brain Delivery of Oligonucleotide Therapeutics Enhanced by Protein Corona-Assisted DNA Cubes.

The systemic delivery of oligonucleotide therapeutics to the brain is challenging but highly desirable for the treatment of brain diseases undruggable with traditional small-molecule drugs. In this study, a set of DNA nanostructures is prepared and screened them to develop a protein corona-assisted platform for the brain delivery of oligonucleotide therapeutics. The biodistribution analysis of intravenously injected DNA nanostructures reveals that a cube-shaped DNA nanostructure (D-Cb) can penetrate the brain-blood barrier (BBB) and reach the brain tissue. The brain distribution level of D-Cb is comparable to that of other previous nanoparticles conjugated with brain-targeting ligands. Proteomic analysis of the protein corona formed on D-Cb suggests that its brain distribution is driven by endothelial receptor-targeting ligands in the protein corona, which mediate transcytosis for crossing the BBB. D-Cb is subsequently used to deliver an antisense oligonucleotide (ASO) to treat glioblastoma multiforme (GBM) in mice. While free ASO is unable to reach the brain, ASO loaded onto D-Cb is delivered efficiently to the brain tumor region, where it downregulates the target gene and exerts an anti-tumor effect on GBM. D-Cb is expected to serve as a viable platform based on protein corona formation for systemic brain delivery of oligonucleotide therapeutics.

Decreased Serum Cocaine- and Amphetamine-Regulated Transcript Level in Internet Gaming Disorder.

OBJECTIVE: Vulnerability to internet gaming disorder (IGD) has increased as internet gaming continues to grow. Cocaine- and amphetamine-regulated transcript (CART) is a hormone that plays a role in reward, anxiety, and stress. The purpose of this study was to identify the role of CART in the pathophysiology of IGD. METHODS: The serum CART levels were measured by enzyme-linked immunosorbent assay, and the associations of the serum CART level with psychological variables were analyzed in patients with IGD (n=31) and healthy controls (HC) (n=42). RESULTS: The serum CART level was significantly lower in the IGD than HC group. The IGD group scored significantly higher than the HC group on the psychological domains of depression, anxiety, the reward response in the Behavioral Activation System and Behavioral Inhibition System. There were no significant correlations between serum CART level and other psychological variables in the IGD group. CONCLUSION: Our results indicate that a decrease in the expression of the serum CART level is associated with the vulnerability of developing IGD. This study supports the possibility that CART is a biomarker in the pathophysiology of IGD.