jp6b12182_si_liveslides.zip (7.38 MB)
Multivalency Effect of TAT-Peptide-Functionalized Nanoparticle in Cellular Endocytosis and Subcellular Trafficking
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posted on 2017-04-26, 11:19 authored by Chumki Dalal, Nikhil R. JanaAlthough
trans-activating transcription (TAT) peptide-functionalized
nanoparticle/polymer/liposome is widely used for cellular transfection
applications, the multivalency (number of attached peptide per particle)
effect on cell uptake mechanism and subcellular targeting performance
is largely unexplored. Here we show that multivalency of nanoparticle
controls the cellular interaction, cellular entry/exit mechanism,
and subcellular targeting performance. We have synthesized TAT-peptide
functionalized quantum dot (QD) of 30–35 nm hydrodynamic diameter
with varied multivalency from 10 to 75 (e.g., QD(TAT)10, QD(TAT)20, QD(TAT)40, QD(TAT)75) and studied the role of multivalency in endocytosis and subcellular
trafficking. We found that both low and high multivalent nanoparticles
enter into cell predominantly via lipid-raft mediated endocytosis
but the higher multivalency of 40 and 75 induces vesicular trapping
followed by exocytosis within 12 h. In contrast, lower multivalency
of 10 and 20 offers efficient trafficking toward perinuclear region
and Golgi apparatus. This work shows the functional role of nanoparticle
multivalency in cellular uptake mechanism and importance of lower
multivalency for efficient subcellular targeting.
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Golgi apparatus12 hMultivalency EffectTAT-peptide functionalized quantum dotSubcellular TraffickingCellular EndocytosisTAT-Peptide-Functionalized Nanoparticlenanoparticle controlscell uptake mechanismtransfection applicationsperinuclear regionQDtrans-activating transcriptionuptake mechanismnanoparticle multivalencysubcellular trafficking
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