PTEN is a critical tumor suppressor frequently dysregulated in cancers. While PTEN mRNA delivery offers a promising path for immunotherapy, current systems have bottlenecks, such as electrostatic loading dependency, inefficient cytosolic delivery, and stability issues.
To overcome these challenges, a research team has developed a biomimetic mRNA delivery platform inspired by natural metal-ion coordination and exosome mechanisms. The system employs adjuvant metal ions, particularly Mn 2+ , to chelate and load PTEN mRNA through mild, non-electrostatic forces. The resulting complex is further encapsulated in a monocyte-macrophage membrane modified with αPD-L1, facilitating tumor targeting and immune evasion.
Key advantages over conventional lipid nanoparticles (LNPs) were demonstrated:
Additionally, through analysis of clinical data, the team linked PTEN expression levels to patient outcomes. They also developed a classification model to help identify patients most likely to benefit from PTEN-based therapy.
This work provides a robust and efficient mRNA delivery platform and strengthens the case for precision immunotherapy in colorectal cancer.
Science Bulletin