title: Endocytic Trafficking of Nanoparticles Delivered by Cell-penetrating Peptides Comprised of Nona-arginine and a Penetration Accelerating Sequence.
abstract: Cell-penetrating peptides (CPPs) can traverse cellular membranes and deliver biologically active molecules into cells. In this study, we demonstrate that CPPs comprised of nona-arginine (R9) and a penetration accelerating peptide sequence (Pas) that facilitates escape from endocytic lysosomes, denoted as PR9, greatly enhance the delivery of noncovalently associated quantum dots (QDs) into human A549 cells. Mechanistic studies, intracellular trafficking analysis and a functional gene assay reveal that endocytosis is the main route for intracellular delivery of PR9/QD complexes. Endocytic trafficking of PR9/QD complexes was monitored using both confocal and transmission electron microscopy (TEM). Zeta-potential and size analyses indicate the importance of electrostatic forces in the interaction of PR9/QD complexes with plasma membranes. Circular dichroism (CD) spectroscopy reveals that the secondary structural elements of PR9 have similar conformations in aqueous buffer at pH 7 and 5. This study of nontoxic PR9 provides a basis for the design of optimized cargo delivery that allows escape from endocytic vesicles.
authors.affiliation: Department of Natural Resources and Environmental Studies, National Dong Hwa University, Hualien, Taiwan.
authors.forename: Betty R
authors.initials: BR
authors.lastname: Liu
authors.forename: Shih-Yen
authors.initials: SY
authors.lastname: Lo
authors.forename: Chia-Chin
authors.initials: CC
authors.lastname: Liu
authors.forename: Chia-Lin
authors.initials: CL
authors.lastname: Chyan
authors.forename: Yue-Wern
authors.initials: YW
authors.lastname: Huang
authors.forename: Robert S
authors.initials: RS
authors.lastname: Aronstam
authors.forename: Han-Jung
authors.initials: HJ
authors.lastname: Lee
mesh_terms: D000072283:A549 Cells; D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D001120:Arginine / Q000737:chemistry*; D057846:Cell-Penetrating Peptides / Q000737:chemistry* / Q000378:metabolism*; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism*; D004705:Endocytosis; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D007700:Kinetics; D008247:Lysosomes / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D021381:Protein Transport; D045663:Quantum Dots / Q000737:chemistry
chemical_list: D000199:Actins; D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D001120:Arginine