Rapid Endolysosomal Escape and Controlled Intracellular
Trafficking of Cell Surface Mimetic Quantum-Dots-Anchored Peptides
and Glycopeptides
- Publication date
- Publisher
Abstract
A novel strategy for the development
of a high performance nanoparticules
platform was established by means of cell surface mimetic quantum-dots
(QDs)-anchored peptides/glycopeptides, which was developed as a model
system for nanoparticle-based drug delivery (NDD) vehicles with defined
functions helping the specific intracellular trafficking after initial
endocytosis. In this paper, we proposed a standardized protocol for
the preparation of multifunctional QDs that allows for efficient cellular
uptake and rapid escaping from the endolysosomal system and subsequent
cytoplasmic molecular delivery to the target cellular compartment.
Chemoselective ligation of the ketone-functionalized hexahistidine
derivative facilitated both efficient endocytic entry and rapid endolysosomal
escape of the aminooxy/phosphorylcholine self-assembled monolayer-coated
QDs (AO/PCSAM-QDs) to the cytosol in various cell lines such as human
normal and cancer cells, while modifications of these QDs with cell-penetrating
arginine-rich peptides showed poor cellular uptake and induced self-aggregation
of AO/PCSAM-QDs. Combined use of hexahistidylated AO/PCSAM-QDs with
serglycine-like glycopeptides, namely synthetic proteoglycan initiators
(PGIs), elicited the entry and controlled intracellular trafficking,
Golgi localization, and also excretion of these nanoparticles, which
suggested that the present approach would provide an ideal platform
for the design of high performance NDD systems