Xentry is a cell-penetrating peptide (CCP) composed only of seven amino acids from the hepatitis B virus: LCLRPVG. By linking with anti-B-raf antibodies and siRNA, Xentry can target and eliminate B-raf-dependent melanoma cells. It can be administered alone or combined with β-galactosidase to deliver substances to most tissues in mice, except circulating blood cells. Xentry is useful for delivering macromolecules such as antibodies, siRNA, and enzymes.

Xentry (10 μM) penetrates adherent cells in an energy-dependent manner, including the cell lines HepG2 (liver), C32 (melanoma), DU145 (prostate), H441 (lung cancer), BT474 (breast), Cos (kidney), and Rin-m5F (pancreatic beta cells), but does not penetrate non-adherent resting blood cells. When conjugated with β-galactosidase (10-20 μM, 4 h), Xentry is internalized by viable HepG2 cells and enters through the multi-ligand glycan pathway. Additionally, Xentry (1 h) effectively delivers antibodies and siRNA to melanoma cells, inducing apoptosis in B-raf dependent melanoma cells.

Within 15 minutes of a single intravenous dose, Cy7-labeled Xentry (2-20 μg/mL) disperses extensively across various tissues, with notable accumulation in epithelial tissues such as the intestines, stomach, and bronchi; 24 hours later, it predominantly remains in the liver and kidneys in Balb/c mice. TAMRA-labeled Xentry (2-100 μg/mL), also administered in a single intravenous dose, effectively delivers macromolecular complexes to multiple tissues in Balb/c mice, particularly concentrating in intestinal epithelial cells and splenic marginal sinuses.