The functionalization of nanoparticles (NPs) with cell penetrating peptides (CPPs) constitutes a breakthrough for the intracellular delivery of therapeutic and diagnostic payloads. In late 1998, a significant cellular uptake of a small protein from the HIV-1 virus, namely TAT peptide (TATp), was observed. Thereafter, research began on design of similarly acting peptides, and the coupling of NPs with these novel CPPs. Here, we describe recent methods used to modify the surface of NPs with CPPs and the in vitro and in vivo effects of such functionalization on the intracellular delivery of various cargos. In particular, we highlight recent advances aimed at reducing the non-selectivity of CPPs and the prevention of their enzymatic cleavage en route to target tissues.
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