Intracellular Delivery of Nanoparticles Mediated by Lactoferricin Cell-Penetrating Peptides in an Endocytic Pathway

Cell-penetrating peptides (CPPs) containing a preponderance of basic amino acids are able to deliver biologically active macromolecules and nanomaterials into live cells. Quantum dots (QDs) are nanoparticles with unique fluorescence properties that have found wide application in biomedical imaging. In this study, we demonstrate transduction of an L6 CPP (RRWQWR) derived from bovine lactoferricin (LFcin) into human lung cancer cells. L6 noncovalently interacts with QDs to form stable complexes. L6/QD complexes enter cells most efficiently when prepared at a nitrogen/phosphate ratio of 60. Mechanistic studies indicate that L6/QD complexes enter cells by endocytosis. Treatment with 1,2-benzisothiazol-3(2H)-one (BIT), an industrial preservative that enhances uptake of certain CPPs, does not affect L6 CPP-mediated protein transduction efficiency. L6 and L6/QD complexes are not cytotoxic. These results indicate that L6 LFcin might be an efficient and safe nanoshuttle for nanoparticles or nanomedicines in biomedical applications.