Liposomes modified with cell-penetrating peptides.A
new approach to drug delivery has recently emerged,
which is based on the use of certain viral proteins that
have the ability to penetrate into cells (the so-called
‘protein transduction’phenomenon). The transactivating
transcriptional activator (TAT) protein from HIV-1
enters various cells when added to the surrounding
media205. Recent data indicate that there is more than
one mechanism used by cell-penetrating peptides and
proteins (CPP) and CPP-mediated intracellular delivery
of various molecules and particles. TAT-mediated
intracellular delivery of large molecules and nanoparticles
occurs through energy-dependent macropinocytosis,
with subsequent enhanced escape from endosome into
the cell cytoplasm206, whereas individual CPPs or CPPconjugated small molecules penetrate cells via electrostatic interactions and hydrogen bonding and and the
penetration does not seem to be associated with metabolic energy (that is, it is a purely physical, not biological,