title: Intracellular Delivery of Luminescent Quantum Dots Mediated by a Virus-Derived Lytic Peptide.
abstract: We describe a new quantum dot (QD)-conjugate prepared with a lytic peptide, derived from a nonenveloped virus capsid protein, capable of bypassing the endocytotic pathways and delivering large amounts of QDs to living cells. The polypeptide, derived from the Nudaurelia capensis Omega virus, was fused onto the C-terminus of maltose binding protein that contained a hexa-HIS tag at its N-terminus, allowing spontaneous self-assembly of controlled numbers of the fusion protein per QD via metal-HIS interactions. We found that the efficacy of uptake by several mammalian cell lines was substantial even for small concentrations (10-100 nM). Upon internalization the QDs were primarily distributed outside the endosomes/lysosomes. Moreover, when cells were incubated with the conjugates at 4 °C, or in the presence of chemical endocytic inhibitors, significant intracellular uptake continued to occur. These findings indicate an entry mechanism that does not involve endocytosis, but rather the perforation of the cell membrane by the lytic peptide on the QD surfaces.
authors.affiliation: Florida State University , Department of Chemistry and Biochemistry, 95 Chieftan Way, Tallahassee, Florida 32306, United States.
authors.forename: Malak
authors.initials: M
authors.lastname: Safi
authors.affiliation: The Scripps Research Institute , Department of Integrative Structural and Computational Biology, MB31, La Jolla, California 92037, United States.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Domitrovic
authors.forename: Anshika
authors.initials: A
authors.lastname: Kapur
authors.affiliation: Florida State University , Department of Chemistry and Biochemistry, 95 Chieftan Way, Tallahassee, Florida 32306, United States.
authors.forename: Naiqian
authors.initials: N
authors.lastname: Zhan
authors.affiliation: Florida State University , Department of Chemistry and Biochemistry, 95 Chieftan Way, Tallahassee, Florida 32306, United States.
authors.forename: Fadi
authors.initials: F
authors.lastname: Aldeek
authors.affiliation: The Scripps Research Institute , Department of Integrative Structural and Computational Biology, MB31, La Jolla, California 92037, United States.
authors.forename: John E
authors.initials: JE
authors.lastname: Johnson
authors.affiliation: Florida State University , Department of Chemistry and Biochemistry, 95 Chieftan Way, Tallahassee, Florida 32306, United States.
authors.forename: Hedi
authors.identifier: 0000-0002-6511-9323
authors.initials: H
authors.lastname: Mattoussi
mesh_terms: D000818:Animals; D002460:Cell Line; D011992:Endosomes / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D049449:Luminescence; D008247:Lysosomes / Q000378:metabolism; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry; D045663:Quantum Dots / Q000008:administration & dosage* / Q000378:metabolism; D014764:Viral Proteins / Q000737:chemistry*
chemical_list: D010455:Peptides; D014764:Viral Proteins