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Liposomes have been widely investigated as a class of promising antibiotic delivery systems for the treatment of life-threatening bacterial infections. However, the inevitable formation of protein corona on the liposomal surface can heavily impact in vivo performance. A better understanding of the effects of protein corona on liposomal behavior can significantly improve antibacterial liposomal drug development. Here, the critical role of protein corona in mediating liposome-bacteria interactions was elucidated. Adsorption of negatively charged protein on cationic liposome weakened electrostatic attraction-enhanced liposomal binding to the bacteria. Cumulative complement deposition on anionic liposome composed of phosphatidylglycerol (DSPG sLip) contributed to a superior binding affinity of DSPG sLip to planktonic bacteria and biofilms, which was exploited to enhance bacteria-targeted drug delivery. In both S. aureus -related osteomyelitis and pneumonia mice models, DSPG sLip was demonstrated as a promising antibiotic nanocarrier for managing MRSA infection, indicating the benefits of lipid composition-based protein corona modulation in liposomal antibiotic delivery for bacterial infection treatment. [ABSTRACT FROM AUTHOR]

Glucose transporter (GLUT)-mediated transcytosis has been validated as an efficient method to cross the blood-brain barrier and enhance brain transport of nanomedicines. However, the transcytosis process remains elusive. Glycopeptide-modified nanodisks (Gly-A7R-NDs), which demonstrated high capacity of brain targeting via GLUT-mediated transcytosis in our previous reports, were utilized to better understand the whole transcytosis process. Gly-A7R-NDs internalized brain capillary endothelial cells mainly via GLUT-mediated/clathrin dependent endocytosis and macropinocytosis. The intracellular Gly-A7R-NDs remained intact, and the main excretion route of Gly-A7R-NDs was lysosomal exocytosis. Glycosylation of nanomedicine was crucial in GLUT-mediated transcytosis, while morphology did not affect the efficiency. This study highlights the pivotal roles of lysosomal exocytosis in the process of GLUT-mediated transcytosis, providing a new impetus to development of brain targeting drug delivery by accelerating lysosomal exocytosis. [ABSTRACT FROM AUTHOR]