Annals of the New York Academy of Sciences
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Ann. N. Y. Acad. Sci. · Nov 2005
Endo-Porter: a novel reagent for safe, effective delivery of substances into cells.
Delivering large molecules into the cytosol of animal cells without damaging the cells has been one of the toughest challenges in biology. Endo-Porter is a weak-base amphiphilic peptide that was designed to deliver morpholino antisense oligomers and other non-ionic substances into the cytosol/nuclear compartment of cells by an endocytosis-mediated process that avoids damaging the plasma membrane of the cell. This prevents the loss of vital cell contents and the attendant high cell toxicity typical of most delivery systems. ⋯ Upon subsequent acidification of the endosome (a natural process) the Endo-Porter contained within that endosome is converted to its poly-cationic form, which acts to permeabilize the endosomal membrane. This acid-induced permeabilization of the endosomal membrane allows any co-endocytosed cargo to pass from the endosome into the cytosol of the cell. This paper describes the basic design strategy used to develop Endo-Porter, test systems used to guide that development, and the effects of various structural parameters, including size and composition of the lipophilic face, size and composition of the weak-base face, and the relationship between peptide length and delivery efficiency in the presence of serum.