Sebastian Leon: “Novel creatine-loaded nanoparticles: A potential therapeutic avenue for creatine transporter deficiency”
SHORT SUMMARY
This work presents a promising approach for future CTD treatment. The nanoparticles we designed, composed of safe materials commonly used in the food industry, and have successfully delivered creatine to CTD-patient cells in a cell culture model. While we still have a lot of work to do, the particles helped CTD-patient cells survive prolonged starvation, demonstrating that our technology can penetrate cells and improve outcomes.
ABSTRACT
Creatine Transporter Deficiency (CTD) is an X-linked disorder characterized by a dysfunctional Creatine Transporter (CrT), leading to impaired creatine uptake and disrupted cerebral energy metabolism. Despite the critical role of creatine in cellular energy balance, effective treatments for CTD are currently lacking. Novel therapeutic approaches, such as gene therapy or nanoscale delivery systems, hold promise for addressing this unmet medical need. In this study, we report the synthesis and characterization of novel creatine-loaded, polyphenol-based particles. Our particles exhibit an impressive loading capacity exceeding 50% and demonstrate no discernible toxicity towards mature hiPSC cortical neurons. Comprehensive characterization employing LC-MS, FTIR, UV-visible spectroscopy, fluorescence spectrophotometry, and Dynamic Light Scattering highlights the distinctive properties of this innovative formulation, laying a solid foundation for its further advancement. FTIR spectroscopy analysis reveals no alterations to creatine, suggesting its loading mechanism relies on Van der Waals forces rather than permanent chemical conjugation. Additionally, fluorescence spectrophotometry indicates a close interaction between creatine and the phenolic compound utilized in the synthesis. Importantly, the synthesized particles are composed of Generally Regarded as Safe (GRAS) materials, ensuring their safety for biomedical applications, and have an average hydrodynamic radius of 318 nm, a zeta-potential of -18 mV, and a polydispersity index of 0.22.