Evaluation of diverse peptidyl motifs for cellular delivery of semiconductor quantum dots Optical Nanosensing in Cells

Gemmill, Kelly Boeneman, Muttenthaler, Markus, Delehanty, James B., Stewart, Michael H., Susumu, Kimihiro, Dawson, Philip E. and Medintz, Igor L. (2013) Evaluation of diverse peptidyl motifs for cellular delivery of semiconductor quantum dots Optical Nanosensing in Cells. Analytical and Bioanalytical Chemistry, 405 19: 6145-6154. doi:10.1007/s00216-013-6982-2


Author Gemmill, Kelly Boeneman
Muttenthaler, Markus
Delehanty, James B.
Stewart, Michael H.
Susumu, Kimihiro
Dawson, Philip E.
Medintz, Igor L.
Title Evaluation of diverse peptidyl motifs for cellular delivery of semiconductor quantum dots Optical Nanosensing in Cells
Journal name Analytical and Bioanalytical Chemistry   Check publisher's open access policy
ISSN 1618-2642
1618-2650
Publication date 2013-07-01
Year available 2013
Sub-type Article (original research)
DOI 10.1007/s00216-013-6982-2
Open Access Status Not yet assessed
Volume 405
Issue 19
Start page 6145
End page 6154
Total pages 10
Place of publication Heidelberg, Germany
Publisher Springer
Language eng
Abstract Cell-penetrating peptides (CPPs) have rapidly become a mainstay technology for facilitating the delivery of a wide variety of nanomaterials to cells and tissues. Currently, the library of CPPs to choose from is still limited, with the HIV TAT-derived motif still being the most used. Among the many materials routinely delivered by CPPs, nanoparticles are of particular interest for a plethora of labeling, imaging, sensing, diagnostic, and therapeutic applications. The development of nanoparticle-based technologies for many of these uses will require access to a much larger number of functional peptide motifs that can both facilitate cellular delivery of different types of nanoparticles to cells and be used interchangeably in the presence of other peptides and proteins on the same surface. Here, we evaluate the utility of four peptidyl motifs for their ability to facilitate delivery of luminescent semiconductor quantum dots (QDs) in a model cell culture system. We find that an LAH4 motif, derived from a membrane-inserting antimicrobial peptide, and a chimeric sequence that combines a sweet arrow peptide with a portion originating from the superoxide dismutase enzyme provide effective cellular delivery of QDs. Interestingly, a derivative of the latter sequence lacking just a methyl group was found to be quite inefficient, suggesting that even small changes can have significant functional outcomes. Delivery was effected using 1 h incubation with cells, and fluorescent counterstaining strongly suggests an endosomal uptake process that requires a critical minimum number or ratio of peptides to be displayed on the QD surface. Concomitant cytoviability testing showed that the QD-peptide conjugates are minimally cytotoxic in the model COS-1 cell line tested. Potential applications of these peptides in the context of cellular delivery of nanoparticles and a variety of other (bio)molecules are discussed.
Formatted abstract
Cell-penetrating peptides (CPPs) have rapidly become a mainstay technology for facilitating the delivery of a wide variety of nanomaterials to cells and tissues. Currently, the library of CPPs to choose from is still limited, with the HIV TAT-derived motif still being the most used. Among the many materials routinely delivered by CPPs, nanoparticles are of particular interest for a plethora of labeling, imaging, sensing, diagnostic, and therapeutic applications. The development of nanoparticle-based technologies for many of these uses will require access to a much larger number of functional peptide motifs that can both facilitate cellular delivery of different types of nanoparticles to cells and be used interchangeably in the presence of other peptides and proteins on the same surface. Here, we evaluate the utility of four peptidyl motifs for their ability to facilitate delivery of luminescent semiconductor quantum dots (QDs) in a model cell culture system. We find that an LAH4 motif, derived from a membrane-inserting antimicrobial peptide, and a chimeric sequence that combines a sweet arrow peptide with a portion originating from the superoxide dismutase enzyme provide effective cellular delivery of QDs. Interestingly, a derivative of the latter sequence lacking just a methyl group was found to be quite inefficient, suggesting that even small changes can have significant functional outcomes. Delivery was effected using 1 h incubation with cells, and fluorescent counterstaining strongly suggests an endosomal uptake process that requires a critical minimum number or ratio of peptides to be displayed on the QD surface. Concomitant cytoviability testing showed that the QD–peptide conjugates are minimally cytotoxic in the model COS-1 cell line tested. Potential applications of these peptides in the context of cellular delivery of nanoparticles and a variety of other (bio)molecules are discussed.
Keyword Cell
Cell-penetrating peptide
Delivery
Endocytosis
Labeling
Metal affinity
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID B112582M
254897
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
 
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