Revealing Angiopep-2/LRP1 Molecular Interaction for Optimal Delivery to Glioblastoma (GBM).

BACKGROUND: The family of synthetic peptide angiopeps, and particularly angiopep-2 (ANG-2) demonstrated the ability preclinically and clinically to shuttle active molecules across the blood-brain barrier (BBB) and selectively toward brain tumor cells. The literature has also proved that the transport occurs through a specific receptor-mediated transcytosis of the peptide by LRP-1 receptors present both on BBB and tumor cell membranes. However, contradictory results about exploiting this promising mechanism to engineer complex delivery systems, such as nanoparticles, are being obtained. METHODOLOGY: For this reason, we applied a molecular docking (MD)-based strategy to investigate the molecular interaction of ANG-2 and the LRP-1 ligand-binding moieties (CR56 and CR17), clarifying the impact of peptide conjugation on its transport mechanism. RESULTS: MD results proved that ANG-2/LRP-1 binding involves the majority of ANG-2 residues, is characterized by high binding energies, and that it is site-specific for CR56 where the binding to 929ASP recalls a transcytosis mechanism, resembling the binding of the receptor to the receptor-associated protein. On the other hand, ANG-2 binding to CR17 is less site-specific but, as proved for apolipoprotein internalization in physiological conditions, it involves the ANG-2 lysin residue. CONCLUSIONS: Overall, our results proved that ANG-2 energetic interaction with the LRP-1 receptor is not hindered if specific residues of the peptide are chemically crosslinked to simple or complex engineered delivery systems.

Multimodal imaging for a theranostic approach in a murine model of B-cell lymphoma with engineered nanoparticles.

Nanoparticles (NPs) are a promising tool for in vivo multimodality imaging and theranostic applications. Hyaluronic acid (HA)-based NPs have numerous active groups that make them ideal as tumor-targeted carriers. The B-lymphoma neoplastic cells express on their surfaces a clone-specific immunoglobulin receptor (Ig-BCR). The peptide A20-36 (pA20-36) selectively binds to the Ig-BCR of A20 lymphoma cells. In this work, we demonstrated the ability of core-shell chitosan-HA-NPs decorated with pA20-36 to specifically target A20 cells and reduce the tumor burden in a murine xenograft model. We monitored tumor growth using high-frequency ultrasonography and demonstrated targeting specificity and kinetics of the NPs via in vivo fluorescent reflectance imaging. This result was also confirmed by ex vivo magnetic resonance imaging and confocal microscopy. In conclusion, we demonstrated the ability of NPs loaded with fluorescent and paramagnetic tracers to act as multimodal imaging contrast agents and hence as a non-toxic, highly specific theranostic system.

Comparing Two Approaches for Thyroidectomy: A Health Technology Assessment through DMAIC Cycle.

Total thyroidectomy is very common in endocrine surgery and the haemostasis can be obtained in different ways across surgery; recently, some devices have been developed to support this surgical phase. In this paper, a health technology assessment is conducted through the define, measure, analyse, improve, and control cycle of the Six Sigma methodology to compare traditional total thyroidectomy with the surgical operation performed through a new device in an overall population of 104 patients. Length of hospital stay, drain output, and time for surgery were considered the critical to qualities in order to compare the surgical approaches which can be considered equal regarding the organizational, ethical, and security impact. Statistical tests (Kolmogorov-Smirnov, t test, ANOVA, Mann-Whitney, and Kruskal-Wallis tests) and visual management diagrams were employed to compare the approaches, but no statistically significant difference was found between them. Considering these results, this study shows that the introduction of the device to perform total thyroidectomy does not guarantee appreciable clinical advantages. A cost analysis to quantify the economic impact of the device into the practice could be a future development. Healthy policy leaders and clinicians who are requested to make decisions regarding the supply of biomedical technologies could benefit from this research.

Fuzzy logic-based clinical decision support system for the evaluation of renal function in post-Transplant Patients.

OBJECTIVES: In the context of the gradual development of artificial intelligence in health care, the clinical decision support systems (CDSS) play an increasing crucial role in improving the quality of the therapeutic and diagnostic efficiency in health care. The fuzzy logic (FL) provides an effective means for dealing with uncertainties in the health decision-making process; therefore, FL-based CDSS becomes a very powerful tool for data and knowledge management, being able to think like an expert clinician. This work proposes an FL-based CDSS for the evaluation of renal function in posttransplant patients. METHOD: Based on the data provided by the Department of Nephrology of the University Hospital Federico II of Naples, a statistical sample is selected according to appropriate inclusion criteria. Four fuzzy inference systems are implemented monitoring the renal function by the level of proteinuria and the glomerular filtration rate (GFR). RESULTS: The systems show an accuracy of more than 90% and the outputs are provided through easy to read graphics, so that physicians can intuitively monitor the patient's clinical status, with the objective to improve drugs dosage and reduce medication errors. CONCLUSIONS: We propose that the CDSSs for the assessment and follow-up of kidney-transplanted patients built in this study are applicable to clinical practice.

Hybrid core shell nanoparticles entrapping Gd-DTPA and 18F-FDG for simultaneous PET/MRI acquisitions.

AIM: Although there has been an improvement in the hardware and software of the PET/MRI system, the development of the nanoprobes exploiting the simultaneous acquisition of the bimodal data is still under investigation. Moreover, few studies on biocompatible and clinically relevant probes are available. This work presents a core-shell polymeric nanocarrier with improved relaxometric properties for simultaneous PET/MRI acquisitions. MATERIALS & METHODS: Core-shell nanoparticles entrapping the Gd-DTPA and 18F-FDG are obtained by a complex coacervation. RESULTS & DISCUSSION: The boosting of r1 of the entrapped Gd-DTPA up to five-times compared with 'free Gd-DTPA', is confirmed by the PET/MRI scan. The sorption of 18F-FDG into the nanoparticles is studied and designed to be integrated downstream for the production of the tracer.