The clinical success of chimeric antigen receptor (CAR) T cell therapy requires scalable, non-invasive strategies for in vivo T cell engineering. Although mRNA delivery offers a promising alternative, lipid-nanoparticle-based carriers show limited efficiency for in vivo T cell transfection and typically require antibody conjugation. Without exogenous stimulation, ERTLNPs intrinsically activated T cells, triggering robust mRNA expression and proliferation. Mechanistically, ERTLNPs engaged the PI3K/AKT/mTOR signalling axis to reprogram T cell metabolism, promoting expansion and restraining exhaustion.
