1 research outputs found
Efficient Subcellular Targeting to the Cell Nucleus of Quantum Dots Densely Decorated with a Nuclear Localization Sequence Peptide
Organelle-targeted drug delivery can enhance the efficiency
of the intracellularly acting drugs and reduce their toxicity. We
generated core–shell type CdSe-ZnS quantum dots (QDs) densely
decorated with NLS peptidic targeting residues using a 3-stage decoration
approach and investigated their endocytosis and nuclear targeting
efficiencies. The diameter of the generated QDs increased following
the individual decoration stages (16.3, 18.9, and 21.9 nm), the ζ-potential
became less negative (−33.2, −17.5, and −11.9
mV), and characteristic changes appeared in the FTIR spectra following
decoration with the linker and NLS peptides. Quantitative analysis
of the last decoration stage revealed that 37.9% and 33.2% of the
alkyne-modified NLS groups that were added to the reaction mix became
covalently attached or adsorbed to the QDs surface, respectively.
These numbers correspond to 63.6 and 55.7 peptides conjugated or adsorbed
to a single QD (the surface density of 42 and 37 conjugated and adsorbed
peptides per 1000 nm<sup>2</sup> of the QDs surface), which is higher
than in the majority of previous studies that reported decoration
efficiencies of formulations intended for nuclear-targeted drug delivery.
QDs decorated with NLS peptides undergo more efficient endocytosis,
as compared to other investigated QDs formulations, and accumulated
to a higher extent in the cell nucleus or in close vicinity to it
(11.9%, 14.6%, and 56.1% of the QDs endocytosed by an average cell
for the QD-COOH, QD-azide, and QD-NLS formulations, respectively).
We conclude that dense decoration of QDs with NLS residues increased
their endocytosis and led to their nuclear targeting (preferential
accumulation in the cells nuclei or in close vicinity to them). The
experimental system and research tools that were used in this study
allow quantitative investigation of the mechanisms that govern the
QDs nuclear targeting and their dependence on the formulation properties.
These findings will contribute to the development of subcellularly
targeted DDSs that will deliver specific drugs to the nuclei of the
target cells and will enhance efficacy and reduce toxicity of these
drugs