Nanoparticle cellular uptake by dendritic wedge peptides: achieving single peptide facilitated delivery

Breger, Joyce C., Muttenthaler, Markus, Delehanty, James B., Thompson, Darren A., Oh, Eunkeu, Susumu, Kimihiro, Deschamps, Jeffrey R., Anderson, George P., Field, Lauren D., Walper, Scott A., Dawson, Philip E. and Medintz, Igor L. (2017) Nanoparticle cellular uptake by dendritic wedge peptides: achieving single peptide facilitated delivery. Nanoscale, 9 29: 10447-10464. doi:10.1039/c7nr03362a


Author Breger, Joyce C.
Muttenthaler, Markus
Delehanty, James B.
Thompson, Darren A.
Oh, Eunkeu
Susumu, Kimihiro
Deschamps, Jeffrey R.
Anderson, George P.
Field, Lauren D.
Walper, Scott A.
Dawson, Philip E.
Medintz, Igor L.
Title Nanoparticle cellular uptake by dendritic wedge peptides: achieving single peptide facilitated delivery
Journal name Nanoscale   Check publisher's open access policy
ISSN 2040-3372
2040-3364
Publication date 2017-08-07
Year available 2017
Sub-type Article (original research)
DOI 10.1039/c7nr03362a
Open Access Status Not yet assessed
Volume 9
Issue 29
Start page 10447
End page 10464
Total pages 18
Place of publication Cambridge, United Kingdom
Publisher Royal Society of Chemistry
Language eng
Abstract Significant efforts are being undertaken to optimize the cargo carrying capacity and especially the cellular delivery efficiency of functionalized nanoparticles for applications in biological research and pharmacological delivery. One approach to increasing nanoparticle surface cargo display capacity is to decrease the number of moieties required for mediating cellular delivery by improving their efficiency. We describe a series of multivalent cell penetrating peptide (CPP) dendrimers that facilitate rapid cellular delivery of prototypical nanoparticle-semiconductor quantum dots (QDs). The modular CPP dendrimers were assembled through an innovative convergent oxime ligation strategy between (Arg) motifs and a dendritic QD-coordination scaffold. Dendrimeric peptides sequentially incorporate a terminal (His) motif for metal-affinity QD coordination, a Pro spacer, a branching poly-lysine scaffold, and wedged display of (Arg) binding motifs with n = 1×, 2×, 4×, 8×, 16× multivalency. QD dendrimer display capacity was estimated using structural simulations and QD-(Arg) conjugates characterized by dynamic light scattering along with surface plasmon resonance-based binding assays to heparan sulfate proteoglycan surfaces. Cellular uptake via endocytosis was confirmed and peptide delivery kinetics investigated as a function of QD-(Arg) conjugate exposure time and QD assembly ratio where cellular viability assays reflected no overt cytotoxicity. The ability of single dendrimer conjugates to facilitate cellular uptake was confirmed for QD-(Arg) repeats along with the ability to deliver >850 kDa of protein cargo per QD. Minimizing the number of CPPs required for cellular uptake is critical for expanding nanoparticle cargo carrying capacity and can allow for inclusion of additional sensors, therapeutics and contrast agents on their surface.
Formatted abstract
Significant efforts are being undertaken to optimize the cargo carrying capacity and especially the cellular delivery efficiency of functionalized nanoparticles for applications in biological research and pharmacological delivery. One approach to increasing nanoparticle surface cargo display capacity is to decrease the number of moieties required for mediating cellular delivery by improving their efficiency. We describe a series of multivalent cell penetrating peptide (CPP) dendrimers that facilitate rapid cellular delivery of prototypical nanoparticle-semiconductor quantum dots (QDs). The modular CPP dendrimers were assembled through an innovative convergent oxime ligation strategy between (Arg9)n motifs and a dendritic QD-coordination scaffold. Dendrimeric peptides sequentially incorporate a terminal (His)6 motif for metal-affinity QD coordination, a Pro9 spacer, a branching poly-lysine scaffold, and wedged display of (Arg9)n binding motifs with n = 1×, 2×, 4×, 8×, 16× multivalency. QD dendrimer display capacity was estimated using structural simulations and QD–(Arg9)1–16 conjugates characterized by dynamic light scattering along with surface plasmon resonance-based binding assays to heparan sulfate proteoglycan surfaces. Cellular uptake via endocytosis was confirmed and peptide delivery kinetics investigated as a function of QD–(Arg9)1–16 conjugate exposure time and QD assembly ratio where cellular viability assays reflected no overt cytotoxicity. The ability of single dendrimer conjugates to facilitate cellular uptake was confirmed for QD–(Arg9)2–16 repeats along with the ability to deliver >850 kDa of protein cargo per QD. Minimizing the number of CPPs required for cellular uptake is critical for expanding nanoparticle cargo carrying capacity and can allow for inclusion of additional sensors, therapeutics and contrast agents on their surface.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Institute for Molecular Bioscience - Publications
 
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Created: Tue, 08 Aug 2017, 00:10:50 EST by System User on behalf of Institute for Molecular Bioscience