Open AccessMultivalency Effect of TAT-Peptide-Functionalized Nanoparticle in Cellular Endocytosis and Subcellular Trafficking
Author(s) -
Chumki Dalal,
Nikhil R. Jana
Publication year - 2017
Publication title -
the journal of physical chemistry. b
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.864
H-Index - 392
eISSN - 1520-6106
pISSN - 1520-5207
DOI - 10.1021/acs.jpcb.6b12182
Subject(s) - endocytosis , golgi apparatus , exocytosis , chemistry , biophysics , peptide , microbiology and biotechnology , transfection , subcellular localization , cell penetrating peptide , nanotechnology , cell , cytoplasm , biology , biochemistry , membrane , materials science , gene
Although 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.