Highly Efficient Delivery of Functional Cargoes by a Novel Cell-Penetrating Peptide Derived from SP140-Like Protein

Cell-penetrating peptides (CPPs) have been successfully applied to deliver various functional macromolecules into cells in recent times. Here, we describe a novel CPP designated as hPP3 (KPKRKRRKKKGHGWSR), which were derived from human nuclear body protein SP140-like protein. The location of hPP3-FITC in cells was investigated using the fluorescence microscopy, and the internalization of hPP3 was quantitatively measured using a fluorescence spectrophotometer. The results showed that hPP3-FITC could enter into culturing cells, following a concentration-, incubation time-, serum-, and temperature-dependent manner. Uptake of hPP3-FITC into cells was significantly enhanced by DMSO pretreatment, and inhibited by heparin and the endocytosis inhibitors (chlorpromazine and sodium azide), while the potent lysosomotropic agent, chloroquine, showed small positive effects on hPP3-FITC penetrating. Moreover, hPP3 could mediate functional GFP, KLA, or NBD penetration. The findings of this study showed that human origin peptide hPP3 has the potential to act as a macromolecular carrier penetrating cellular membranes and promising delivery peptide as drug delivery vectors.