Abstract
AbstractEndosomal escape remains a central issue limiting the high protein expression of mRNA therapeutics. Here, we present second near‐infrared (NIR‐II) lipid nanoparticles (LNPs) containing pH activatable NIR‐II dye conjugated lipid (Cy‐lipid) for potentiating mRNA delivery efficiency via a stimulus‐responsive photothermal‐promoted endosomal escape delivery (SPEED) strategy. In acidic endosomal microenvironment, Cy‐lipid is protonated and turns on NIR‐II absorption for light‐to‐heat transduction mediated by 1064 nm laser irradiation. Then, the heat‐promoted LNPs morphology change triggers rapid escape of NIR‐II LNPs from the endosome, allowing about 3‐fold enhancement of enhanced green fluorescent protein (eGFP) encoding mRNA translation capacity compared to the NIR‐II light free group. In addition, the bioluminescence intensity induced by delivered luciferase encoding mRNA in the mouse liver region shows positive correlation with incremental radiation dose, indicating the validity of the SPEED strategy.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
