The Biology of Endosomal Escape: Strategies for Enhanced Delivery of Therapeutics

Intracellular delivery of biomolecules is essential to the success of modern therapeutics, yet endosomal entrapment remains a critical barrier to efficacy, and this has been highlighted with the push toward lipid nanoparticle (LNP) therapeutic delivery. Following cellular uptake, most cargo becomes sequestered in endosomes, where it is vulnerable to degradation or exocytosis, unless effective escape mechanisms are triggered. Here, we examine how the efficiency of cellular uptake and the ability to breach endosomal membranes jointly determine the bioavailability and functional delivery of therapeutic agents. We explore natural strategies evolved by pathogens, including membrane fusion, pore formation, and lipid…

• LT
  La Trobe University
• AR
  Australian Research Council

  Award: FL210100107
• NH
  National Health and Medical Research Council

  Award: APP2033787