ABSTRACT
To investigate the in vivo ablation characteristics of a microwave ablation antenna in the livers of humans with tumors, a retrospective analysis of the ablation zones was conducted after applying Emprint microwave ablation systems for treatment. Percutaneous microwave ablations performed between January 2022 and September 2022 were included in this study. Subsequently, immediate post-ablation echography images were subjected to retrospective evaluation to state the long ablated diameter, short ablated diameter, and volume. The calculated ablation lengths and volume indices were then compared between in vivo and ex vivo results obtained from laboratory experiments conducted on porcine liver. The ex vivo data showed a good correlation between energy delivered and both increasing ablated dimensions (both p < 0.001) and volume (p < 0.001). The in vivo data showed a good correlation for dimensions (p = 0.037 and p = 0.019) and a worse correlation for volume (p = 0.142). When comparing ex vivo and in vivo data for higher energies, the ablated volumes grew much more rapidly in ex vivo cases compared to in vivo ones. Finally, a set of correlations to scale ex vivo results with in vivo ones is presented. This phenomenon was likely due to the absence of perfusion, which acts as a cooling system.
ABSTRACT
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.