Polymer/magnetite carriers functionalized by HER2-DARPin: Avoiding lysosomes during internalization and controlled toxicity of doxorubicin by focused ultrasound induced release.

Nanomedicine has revolutionized the available treatment options during the last decade, but poor selectivity of targeted drug delivery and release is still poses a challenge. In this study, doxorubicin (DOX) and magnetite nanoparticles were encapsulated by freezing-induced loading, coated with polymeric shell bearing two bi-layers of polyarginine/dextran sulphate and finally modified with HER2-specific DARPin proteins. We demonstrated that the enhanced cellular uptake of these nanocarriers predominantly occurs by SKOV-3 (HER2+) cells, in comparison to CHO (HER2-) cells, together with the controlled DOX release using low intensity focused ultrasound (LIFU). In addition, a good ability of DARPin+ capsules to accumulate in the tumor and the possibility of combination therapy with LIFU were demonstrated. A relatively high sensitivity of the obtained nanocarriers to LIFU and their preferential interactions with mitochondria in cancer cells make these carriers promising candidates for cancer treatment, including novel approaches to overcome drug resistance.

[Role of magnetic resonance imaging in the early diagnosis of cognitive impairments in patients with type 1 diabetes mellitus].

OBJECTIVE: To assess the role of brain magnetic resonance imaging (MRI) in patients with type 1 diabetes mellitus (DMI) in relation to clinical, metabolic, and psychoneurological disorders. MATERIAL AND METHODS: Fifty-eight patients aged 16 to 30 years with DM1 were examined; a control group consisted of 29 healthy young people matched by gender and age. Their examination involved clinical, metabolic, and psychological testing. The quality of life was assessed using the general Medical Outcomes Study Short Form (MOS SF-36) and the specific Audit-Dependent Quality of Life (AdDQoL). The Montreal Cognitive Assessment (MoCa test) was employed to screen for cognitive impairments. All the patients were advised by a neurologist. Brain MRI using a 1.0 T Siemens Magnetom scanner was carried out to evaluate structural changes in the central nervous system. RESULTS: The examination of the patients with DM1 revealed the signs of grey matter atrophy, enlarged Virchow-Robin spaces, white matter injury, which correlated with the presence of chronic hyperglycemia, cognitive impairments, and microvascular complications. CONCLUSIONS: Routine brain MRI is best carried out in patients with DMI and poor disease control to timely implement therapeutic-and-prophylactic measures for preventing cognitive impairments and improving the quality of life.

[The level of neurospecific proteins in patients with type 1 diabetes mellitus and cognitive disorders].

Type I diabetes mellitus (DM1) is a widespread metabolic disease ofsocial significance due to early disability in youngpatients and reduced life expectancy. One of the DMI complications is CNS lesions resulting in cognitive dysfunction mediated through metabolic disorders. This condition can be partly or completely reversed if diagnosed and treated'at an early stage. The aim of this study was to determine the level ofneurospecific proteins in 58 patients aged 16-30years with type I diabetes mellitus and cognitive disorders in comparison with 29 healthy controls of simnilar age. All the participants underwent neuropsychological testing based on the Montreal scale for rapid screening of cognitive disorders (MoCA-test). Protein S100, glial fibrillary acidic protein, and myelin basic protein served as early markers of cognitive dysfunction. The study revealed an enhanced level of neurospecific proteins that correlated with hyperglycemia and cognitive deficit (MoCA score 26).