How Individual Building Blocks Help Cell-Penetrating Peptides Cross Cell Barriers

Cell-penetrating peptides (CPPs) face significant delivery efficiency challenges due to cellular barriers.

• CPPs struggle with low delivery efficiency compared to other non-viral systems because of obstacles like the plasma membrane and endosomal acidification.
• The plasma membrane acts as a key barrier regulating biomolecule entry into cells.
• Certain functional groups, especially basic amino acids, may enhance the ability of CPPs to penetrate cellular barriers.
• Histidine is associated with improved endosomal escape for CPPs after internalization.
• Nuclear localization signals could increase the potential for CPPs to enter the nucleus.
• The position and type of specific amino acids within a CPP are crucial for overcoming cellular barriers and enhancing biomolecular delivery.

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