2 research outputs found
Nanomotor-Enabled pH-Responsive Intracellular Delivery of Caspase-3: Toward Rapid Cell Apoptosis
Direct
and efficient intracellular delivery of enzymes to cytosol
holds tremendous therapeutic potential while remaining an unmet technical
challenge. Herein, an ultrasound (US)-propelled nanomotor approach
and a high-pH-responsive delivery strategy are reported to overcome
this challenge using caspase-3 (CASP-3) as a model enzyme. Consisting
of a gold nanowire (AuNW) motor with a pH-responsive polymer coating,
in which the CASP-3 is loaded, the resulting nanomotor protects the
enzyme from release and deactivation prior to reaching an intracellular
environment. However, upon entering a cell and exposure to the higher
intracellular pH, the polymer coating is dissolved, thereby directly
releasing the active CASP-3 enzyme to the cytosol and causing rapid
cell apoptosis. <i>In vitro</i> studies using gastric cancer
cells as a model cell line demonstrate that such a motion-based active
delivery approach leads to remarkably high apoptosis efficiency within
a significantly shorter time and with a lower amount of CASP-3 compared
to other control groups not involving US-propelled nanomotors. For
instance, the reported nanomotor system can achieve 80% apoptosis
of human gastric adenocarcinoma cells within only 5 min, which dramatically
outperforms other CASP-3 delivery approaches. These results indicate
that the US-propelled nanomotors may act as a powerful vehicle for
cytosolic delivery of active therapeutic proteins, which would offer
an attractive means to enhance the current landscape of intracellular
protein delivery and therapy. While CASP-3 is selected as a model
protein in this study, the same nanomotor approach can be readily
applied to a variety of different therapeutic proteins
Nanomotor-Enabled pH-Responsive Intracellular Delivery of Caspase-3: Toward Rapid Cell Apoptosis
Direct
and efficient intracellular delivery of enzymes to cytosol
holds tremendous therapeutic potential while remaining an unmet technical
challenge. Herein, an ultrasound (US)-propelled nanomotor approach
and a high-pH-responsive delivery strategy are reported to overcome
this challenge using caspase-3 (CASP-3) as a model enzyme. Consisting
of a gold nanowire (AuNW) motor with a pH-responsive polymer coating,
in which the CASP-3 is loaded, the resulting nanomotor protects the
enzyme from release and deactivation prior to reaching an intracellular
environment. However, upon entering a cell and exposure to the higher
intracellular pH, the polymer coating is dissolved, thereby directly
releasing the active CASP-3 enzyme to the cytosol and causing rapid
cell apoptosis. <i>In vitro</i> studies using gastric cancer
cells as a model cell line demonstrate that such a motion-based active
delivery approach leads to remarkably high apoptosis efficiency within
a significantly shorter time and with a lower amount of CASP-3 compared
to other control groups not involving US-propelled nanomotors. For
instance, the reported nanomotor system can achieve 80% apoptosis
of human gastric adenocarcinoma cells within only 5 min, which dramatically
outperforms other CASP-3 delivery approaches. These results indicate
that the US-propelled nanomotors may act as a powerful vehicle for
cytosolic delivery of active therapeutic proteins, which would offer
an attractive means to enhance the current landscape of intracellular
protein delivery and therapy. While CASP-3 is selected as a model
protein in this study, the same nanomotor approach can be readily
applied to a variety of different therapeutic proteins