Decompression Process of Glycerol Shock Treatment Can Overcome Endo-Lysosomal Barriers for Intracellular Delivery

[Image: see text] The glycerol shock treatment has been used to improve the calcium phosphate transfection efficacy for several decades because of its high effectiveness and low toxicity. However, the mechanism of glycerol shock treatment is still obscure. In this study, the endo-lysosomal leakage assay demonstrated that the decompression process of glycerol shock treatment could enhance endo-lysosomal membrane permeabilization, which resulted in facilitating endo-lysosomal escape for effective intracellular delivery. The enhanced decompression treatment derived from glycerol shock treatment could increase the change of osmotic pressure further, which showed higher efficacy for intracellular delivery. Herein, we speculated that the endo-lysosomal swelling originated from the decompression process of glycerol shock treatment could cause endo-lysosomal damage.