Lipo-oligoarginine-based intracellular delivery.

Efficient cellular delivery, including plasma membrane permeability and intracellular metabolic stability, is a crucial factor determining the success of therapeutic agents. Cell-penetrating peptides (CPPs) have been widely used for the intracellular delivery of various bioactive molecules into cells to modify cellular functions. We have developed an improved CPP-based cellular delivery vector, named lipo-oligoarginine peptide (LOAP), by conjugating an oligoarginine peptide with a fatty acid moiety. The prepared LOAPs were further stabilized by introducing different combinations of D-Arg residues into the peptide backbone and were systematically evaluated for their membrane-penetrating properties and metabolic stabilities in cells.