RESUMO
The 'enzyme prodrug therapy' represents a promising strategy to overcome limitations of current cancer treatments by the systemic administration of prodrugs, converted by a foreign enzyme into an active anticancer compound directly in tumor sites. One example is D-amino acid oxidase (DAAO), a dimeric flavoenzyme able to catalyze the oxidative deamination of D-amino acids with production of hydrogen peroxide, a reactive oxygen species (ROS), able to favor cancer cells death. A DAAO variant containing five aminoacidic substitutions (mDAAO) was demonstrated to possess a better therapeutic efficacy under low O2 concentration than wild-type DAAO (wtDAAO). Recently, aiming to design promising nanocarriers for DAAO, multi-walled carbon nanotubes (MWCNTs) were functionalized with polyethylene glycol (PEG) to reduce their tendency to aggregation and to improve their biocompatibility. Here, wtDAAO and mDAAO were adsorbed on PEGylated MWCNTs and their activity and cytotoxicity were tested. While PEG-MWCNTs-DAAOs have shown a higher activity than pristine MWCNTs-DAAO (independently on the DAAO variant used), PEG-MWCNTs-mDAAO showed a higher cytotoxicity than PEG-MWCNTs-wtDAAO at low O2 concentration. In order to evaluate the nanocarriers' biocompatibility, PEG-MWCNTs-DAAOs were incubated in human serum and the composition of protein corona was investigated via nLC-MS/MS, aiming to characterize both soft and hard coronas. The mDAAO variant has influenced the bio-corona composition in both number of proteins and presence of opsonins and dysopsonins: notably, the soft corona of PEG-MWCNTs-mDAAO contained less proteins and was more enriched in proteins able to inhibit the immune response than PEG-MWCNTs-wtDAAO. Considering the obtained results, the PEGylated MWCNTs conjugated with the mDAAO variant seems a promising candidate for a selective antitumor oxidative therapy: under anoxic-like conditions, this novel drug delivery system showed a remarkable cytotoxic effect controlled by the substrate addition, against different tumor cell lines, and a bio-corona composition devoted to prolong its blood circulation time, thus improving the drug's biodistribution. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03568-1.
RESUMO
Introduction: Digital transformation and technological innovation which have influenced several areas of social and productive life in recent years, are now also a tangible and concrete reality in the vast and strategic sector of public healthcare. The progressive introduction of digital technologies and their widespread diffusion in many segments of the population undoubtedly represent a driving force both for the evolution of care delivery methods and for the introduction of new organizational and management methods within clinical structures. Methods: The CS Clinical Engineering of the "Spedali Civili Hospital in Brescia" decided to design a path that would lead to the development of a software for the management of biomedical technologies within its competence inside the hospital. The ultimate aim of this path stems from the need of Clinical Engineering Department to have up-to-date, realistic, and systematic control of all biomedical technologies present in the company. "Spedali Civili Hospital in Brescia" is not just one of the most important corporate realities in the city, but it is also the largest hospital in Lombardy and one of the largest in Italy. System development has followed the well-established phases: requirement analysis phase, development phase, release phase and evaluating and updating phase. Results: Finally, cooperation between the various figures involved in the multidisciplinary working group led to the development of an innovative management software called "SIC Brescia". Discussion: The contribution of the present paper is to illustrate the development of a complex implementation model for the digitization of processes, information relating to biomedical technologies and their management throughout the entire life cycle. The purpose of sharing this path is to highlight the methodologies followed for its realization, the results obtained and possible future developments. This may enable other realities in the healthcare context to undertake the same type of pathway inspired by an accomplished model. Furthermore, future implementation and data collection related to the proposed Key Performance Indicators, as well as the consequent development of new operational management models for biomedical technologies and maintenance processes will be possible. In this way, the Clinical Risk Management concept will also be able to evolve into a more controlled, safe, and efficient system for the patient and the user.