Intracellular delivery of quantum dots mediated by a histidine- and arginine-rich HR9 cell-penetrating peptide through the direct membrane translocation mechanism

Abstract Functional peptides that transfer biomaterials, such as semiconductor quantum dots (QDs), into cells in biomaterial research have been developed in recent years. Delivery of QDs conjugated with cell-penetrating peptides (CPPs) into cells by the endocytic pathway was problematic in biomedica...

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Bibliographic Details
Published in:Biomaterials 2011-05, Vol.32 (13), p.3520-3537
Main Authors: Liu, Betty R, Huang, Yue-wern, Winiarz, Jeffrey G, Chiang, Huey-Jenn, Lee, Han-Jung
Format: Article
Language:English
Subjects:
Advanced Basic Science
Arginine - chemistry
Biomaterials
Biomedical materials
Cell Line, Tumor
Cell-penetrating peptides (CPPs)
Cell-Penetrating Peptides - chemistry
Cell-Penetrating Peptides - metabolism
Cellular internalization
Dentistry
Ethyl alcohol
Flow Cytometry
Histidine - chemistry
Humans
Membranes
Microscopy, Confocal
Pathways
Peptides
Protein transduction domains (PTDs)
Quantum Dots
Quantum dots (QDs)
Semiconductor
Semiconductors
Surgical implants
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Summary:Abstract Functional peptides that transfer biomaterials, such as semiconductor quantum dots (QDs), into cells in biomaterial research have been developed in recent years. Delivery of QDs conjugated with cell-penetrating peptides (CPPs) into cells by the endocytic pathway was problematic in biomedical applications because of lysosomal trapping. Here, we demonstrate that histidine- and arginine-rich CPPs (HR9 peptides) stably and noncovalently combined with QDs are able to enter into cells in an extremely short period (4 min). Interrupting both F-actin polymerization and active transport did not inhibit the entry of HR9/QD complexes into cells, indicating that HR9 penetrates cell membrane directly. Subcellular colocalization studies indicated that QDs delivered by HR9 stay in cytosol without any organelle capture. Dimethyl sulphoxide, ethanol and oleic acid, but not pyrenebutyrate, enhanced HR9-mediated intracellular delivery of QDs by promoting the direct membrane translocation pathway. HR9 and HR9/QDs were not cytotoxic. These findings suggest that HR9 could be an efficient carrier to deliver drugs without interfering with their therapeutic activity.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2011.01.041