RESUMEN
Glioblastoma is the most malignant and frequently occurring type of brain tumors in adults. Its treatment has been greatly hampered by the difficulty to achieve effective therapeutic concentration in the tumor sites due to its location and the blood-brain barrier. Intranasal administration has emerged as an alternative for drug delivery into the brain though mucopenetration, and rapid mucociliary clearance still remains an issue to be solved before its implementation. To address these issues, based on the intriguing properties of proteins secreted by mussels, polyphenol and catechol functionalization has already been used to promote mucopenetration, intranasal delivery and transport across the blood-brain barrier. Thus, herein we report the synthesis and study of complex 1, a Pt(IV) prodrug functionalized with catecholic moieties. This complex considerably augmented solubility in contrast to cisplatin and showed a comparable cytotoxic effect on cisplatin in HeLa, 1Br3G and GL261 cells. Furthermore, preclinical in vivo therapy using the intranasal administration route suggested that it can reach the brain and inhibit the growth of orthotopic GL261 glioblastoma. These results open new opportunities for catechol-bearing anticancer prodrugs in the treatment for brain tumors via intranasal administration.
RESUMEN
The cognitive effort associated with remembering (R) vs forgetting (F) neutral and negative words was analyzed through a visual detection task integrated in an item-method directed forgetting task. Thirty-three younger adults participated in the experiment while their electrophysiological activity was registered in the study phase. The results shown: (1) negative words evoked more positive ERPs than neutral words on frontal regions, suggesting a preferential processing of negative words. (2) F-cues evoked more positive ERPs than R-cues did for neutral rather than negative words between 500 and 900 ms. This effect could reflect the difficulty in implementing inhibitory mechanisms on negative words. (3) At visual detection task, RTs for post-F probes were longer than for post-R probes. In 350-550 ms time window, ERPs were more positive for post-F probes than post-R probes in over right frontal regions and left medial parietal regions. Additionally, larger P2 were evoked by post-F negative probes than by post-R negative and post-F neutral ones. (4) In recognition test, participants recognized more negative TBF words than neutral ones. The ERP and behavioral results indicate that forgetting is more difficult than remembering, especially when words have a negative content, which implies a greater recruitment of parietal and frontal regions.
