A Metabolite Co-Delivery Strategy to Improve mRNA Lipid Nanoparticle Delivery

ACS Applied Materials & Interfaces, Год журнала: 2025, Номер unknown

Опубликована: Апрель 24, 2025

Lipid nanoparticles (LNPs) effectively protect mRNA and facilitate its entry into target cells for protein synthesis. Despite these successes, cellular alone may not be enough optimal expression, as translation also depends on the availability of essential metabolites, including metabolic energy sources, coenzymes, amino acids. Without adequate less efficient, potentially leading to higher dosing requirements or poorer therapeutic outcomes LNP therapies. To address this, we develop a metabolite co-delivery strategy by encapsulating metabolites within LNPs, hypothesizing that our approach can uniformly improve delivery. Instead adding fifth component organic phase, involves mixing with payload in aqueous while maintaining molar ratio components phase during formulation. We verify vitro vivo, highlighting broad applicability through mechanism efficacy studies across multiple cell lines, physiological conditions, such normoxia (i.e., 21% oxygen), hypoxia 1% mice. Taken collectively, anticipate serve generalizable enhance vivo expression using offering study treatment disease.

Язык: Английский

The Promise of mRNA Vaccines in Cancer Treatment: Technology, Innovations, Applications, and Future Directions

Critical Reviews in Oncology/Hematology, Год журнала: 2025, Номер unknown, С. 104772 - 104772

Опубликована: Май 1, 2025

Язык: Английский