2 research outputs found
Ultrasound-Responsive Nanodroplet-Based Targeted Therapy via Conversion to Microbubbles
Ultrasound-based
therapy is appealing as it can be used
via a wireless
approach at remote parts of the body including the brain. Microbubbles
are commonly used in such therapy due to their highly sound-responsive
property. However, the larger size of microbubbles limits selective
targeting in vitro/in vivo. Here,
we report the design of nanodroplets of 70–130 nm in size that
can be easily converted to microbubbles via ultrasound exposure. The
advantage of this approach is that smaller nanodroplets can be used
for cell/subcellular targeting, and next, they can be used for therapy
by converting to microbubbles. More specifically, folate/dopamine-terminated
perfluorohexane nanodroplets are designed that are loaded with a molecular
drug. These nanodroplets are used for selective cell targeting, followed
by ultrasound-induced microbubble conversion that is associated with
drug release and intracellular reactive oxygen species generation.
This approach has been used for selective cell therapy applications.
The designed nanodroplet and approach can be used for the enhanced
therapeutic performance of existing drugs
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