On March 02th, our recently work "Rational design of rigid mRNA folding architecture to enhance intracellular processing and protein production" was published on Nature Nanotechnology (2026, doi: org/10.1038/s41565-025-02114-9). Our laboratory has focused on nanomedicine and gene therapy. Here we develop a metal-ion-assisted RNA folding (MARF) strategy which affects the global folding state of RNA molecules and specific metal ions that can increase protein production have been discovered. Specifically, MARF altered the mechanical cues of mRNA-based lipid nanoparticles (LNPs) and the surrounding cell membrane, thus regulating intracellular processing and the physiological fate of delivered mRNA. MARF achieved significantly higher protein expression, due not only to enhanced cytosolic delivery but also the accumulation and sequestration of LNPs in hepatocytes that lead to a longer half-life (ninefold) and the higher expression (7.3-fold) of delivered mRNA compared with control mRNA Overall, this work provides a new MARF technology for more effective mRNA therapy and highlights the potential of mechanical cues in designing nanoparticles for improved mRNA delivery.