3 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
Fluorescence Energy Transfer from Doped to Undoped Quantum Dots
We report here the fluorescence energy
transfer between two types
of inorganic semiconductor nanocrystals: one is doped (d-dots) with
optically active transition metal ion and other one is the undoped
quantum dots (q-dots). While the two types of undoped quantum dots
do not show significant energy transfer, the doped quantum dots under
similar conditions show efficient energy transfer to the undoped one.
The difference in the lifetime makes the doped quantum dots as donor
for quantum dots. Exploring Cu-doped and Mn-doped d-dots as donor
with the suitable size of CdSe q-dots as acceptor, we report here
a detailed study of d-dot to q-dot energy transfer and investigate
the possible mechanism
Acidic pH-Triggered Release of Doxorubicin from Ligand-Decorated Polymeric Micelles Potentiates Efficacy against Cancer Cells
Current chemotherapeutic strategies against various intractable
cancers are futile due to inefficient delivery, poor bioavailability,
and inadequate accumulation of anticancer drugs in the diseased site
with toxicity caused to the healthy neighboring cells. Drug delivery
systems aiming to deliver effective therapeutic concentrations to
the site of action have emerged as a promising approach to address
the above-mentioned issues. Thus, as several receptors have been identified
as being overexpressed on cancer cells including folate receptor (FR),
where up to 100–300 times higher overexpression is shown in
cancer cells compared to healthy cells, approximately 1–10
million receptor copies per cancer cell can be targeted by a folic
acid (FA) ligand. Herein, we developed FA-decorated and doxorubicin-conjugated
polymeric micelles of 30 nm size. The hydrophilic block comprises
poly(ethylene glycol) units, and the hydrophobic block contains aspartic
acid. Decoration of FA on the micelle surface induces ligand–receptor
interaction, resulting in enhanced internalization into the cancer
cell and inside the endolysosomal compartment. Under acidic pH, the
micelle structure is disrupted and the hydrazone bond is cleaved,
which covalently binds the doxorubicin with the hydrophobic backbone
of the polymer and release the drug. We observed that the cellular
uptake and nuclear colocalization of the targeted micelle are 2–4
fold higher than the control micelle at various incubation times in
FR-overexpressed various cancer cell lines (KB, HeLa, and C6). These
results indicate significant prospects for anticancer therapy as an
effective and translational treatment strategy