6 research outputs found
Polyethylenimine-Dermatan Sulfate Complex, a Bioactive Biomaterial with Unique Toxicity to CD146-Positive Cancer Cells
We
report unique bioactivity of a polycation-polyanion complex
with potential utility for cancer therapy. A complex of disulfide-cross-linked
polyethylenimine (CLPEI), a polycation used for gene complexation,
and dermatan sulfate (DS), an anionic polysaccharide to shield excessive
cationic charge of the former, has toxicity to a specific group of
cancer cell lines, including B16-F10 murine melanoma, A375SM human
melanoma, and PC-3 human prostate cancer cells. These CLPEI-DS-sensitive
cells express CD146, which binds to the complex via interaction with
DS. There is a positive correlation between toxicity and intracellular
level of CLPEI, indicating that the CLPEI-DS-sensitivity is attributable
to the increased cellular uptake of CLPEI mediated by the DS-CD146
interactions. In vitro studies show that CLPEI-DS complex causes G<sub>0</sub>/G<sub>1</sub> phase arrest and apoptotic cell death. In syngeneic
and allograft models of B16-F10 melanoma, CLPEI-DS complex administered
with a subtoxic level of doxorubicin potentiates the chemotherapeutic
effect of the drug by loosening tumor tissues. Given the unique toxicity,
CLPEI-DS complex may be a useful carrier of gene or chemotherapeutics
for the therapy of CD146-positive cancers
Tumor-Targeting Transferrin Nanoparticles for Systemic Polymerized siRNA Delivery in Tumor-Bearing Mice
Transferrin (TF) is widely used as
a tumor-targeting ligand for
the delivery of anticancer drugs because the TF receptor is overexpressed
on the surface of various fast-growing cancer cells. In this article,
we report on TF nanoparticles as an siRNA delivery carrier for in
vivo tumor-specific gene silencing. To produce siRNA carrying TF nanoparticles
(NPs), both TF and siRNA were chemically modified with sulfhydryl
groups that can build up self-cross-linked siRNA-TF NPs. Self-polymerized
5′-end thiol-modified siRNA (poly siRNA, psi) and thiolated
transferrin (tTF) were spontaneously cross-linked to form stable NPs
(psi-tTF NPs) under optimized conditions, and they could be reversibly
degraded to release functional monomeric siRNA molecules under reductive
conditions. Receptor-mediated endocytosis of TF induced rapid tumor-cell-specific
uptake of the psi-tTF NPs, and the internalized NPs resulted in a
downregulation of the target protein in red-fluorescent-protein-expressing
melanoma cancer cells (RFP/B16F10) with negligible cytotoxicity. After
systemic administration, the psi-tTF NPs showed marked accumulation
at the tumor, leading to successful target-gene silencing in vivo.
This psi-tTF NP system provided a safe and effective strategy for
in vivo systemic siRNA delivery for cancer therapy
Bioorthogonal Copper Free Click Chemistry for Labeling and Tracking of Chondrocytes <i>In Vivo</i>
Establishment
of an appropriate cell labeling and tracking method
is essential for the development of cell-based therapeutic strategies.
Here, we are introducing a new method for cell labeling and tracking
by combining metabolic gylcoengineering and bioorthogonal copper-free
Click chemistry. First, chondrocytes were treated with tetraacetylated
N-azidoacetyl-d-mannosamine (Ac<sub>4</sub>ManNAz) to generate
unnatural azide groups (-N<sub>3</sub>) on the surface of the cells.
Subsequently, the unnatural azide groups on the cell surface were
specifically conjugated with near-infrared fluorescent (NIRF) dye-tagged
dibenzyl cyclooctyne (DBCO-650) through bioorthogonal copper-free
Click chemistry. Importantly, DBCO-650-labeled chondrocytes presented
strong NIRF signals with relatively low cytotoxicity and the amounts
of azide groups and DBCO-650 could be easily controlled by feeding
different amounts of Ac<sub>4</sub>ManNAz and DBCO-650 to the cell
culture system. For the <i>in vivo</i> cell tracking, DBCO-650-labeled
chondrocytes (1 × 10<sup>6</sup> cells) seeded on the 3D scaffold
were subcutaneously implanted into mice and the transplanted DBCO-650-labeled
chondrocytes could be effectively tracked in the prolonged time period
of 4 weeks using NIRF imaging technology. Furthermore, this new cell
labeling and tracking technology had minimal effect on cartilage formation <i>in vivo</i>
Bioorthogonal Copper Free Click Chemistry for Labeling and Tracking of Chondrocytes <i>In Vivo</i>
Establishment
of an appropriate cell labeling and tracking method
is essential for the development of cell-based therapeutic strategies.
Here, we are introducing a new method for cell labeling and tracking
by combining metabolic gylcoengineering and bioorthogonal copper-free
Click chemistry. First, chondrocytes were treated with tetraacetylated
N-azidoacetyl-d-mannosamine (Ac<sub>4</sub>ManNAz) to generate
unnatural azide groups (-N<sub>3</sub>) on the surface of the cells.
Subsequently, the unnatural azide groups on the cell surface were
specifically conjugated with near-infrared fluorescent (NIRF) dye-tagged
dibenzyl cyclooctyne (DBCO-650) through bioorthogonal copper-free
Click chemistry. Importantly, DBCO-650-labeled chondrocytes presented
strong NIRF signals with relatively low cytotoxicity and the amounts
of azide groups and DBCO-650 could be easily controlled by feeding
different amounts of Ac<sub>4</sub>ManNAz and DBCO-650 to the cell
culture system. For the <i>in vivo</i> cell tracking, DBCO-650-labeled
chondrocytes (1 × 10<sup>6</sup> cells) seeded on the 3D scaffold
were subcutaneously implanted into mice and the transplanted DBCO-650-labeled
chondrocytes could be effectively tracked in the prolonged time period
of 4 weeks using NIRF imaging technology. Furthermore, this new cell
labeling and tracking technology had minimal effect on cartilage formation <i>in vivo</i>
pH-Controlled Gas-Generating Mineralized Nanoparticles: A Theranostic Agent for Ultrasound Imaging and Therapy of Cancers
We report a theranostic nanoparticle that can express ultrasound (US) imaging and simultaneous therapeutic functions for cancer treatment. We developed doxorubicin-loaded calcium carbonate (CaCO<sub>3</sub>) hybrid nanoparticles (DOX-CaCO<sub>3</sub>-MNPs) through a block copolymer templated <i>in situ</i> mineralization approach. The nanoparticles exhibited strong echogenic signals at tumoral acid pH by producing carbon dioxide (CO<sub>2</sub>) bubbles and showed excellent echo persistence. <i>In vivo</i> results demonstrated that the DOX-CaCO<sub>3</sub>-MNPs generated CO<sub>2</sub> bubbles at tumor tissues sufficient for echogenic reflectivity under a US field. In contrast, the DOX-CaCO<sub>3</sub>-MNPs located in the liver or tumor-free subcutaneous area did not generate the CO<sub>2</sub> bubbles necessary for US contrast. The DOX-CaCO<sub>3</sub>-MNPs could also trigger the DOX release simultaneously with CO<sub>2</sub> bubble generation at the acidic tumoral environment. The DOX-CaCO<sub>3</sub>-MNPs displayed effective antitumor therapeutic activity in tumor-bearing mice. The concept described in this work may serve as a useful guide for development of various theranostic nanoparticles for US imaging and therapy of various cancers
Bioorthogonal Copper Free Click Chemistry for Labeling and Tracking of Chondrocytes <i>In Vivo</i>
Establishment
of an appropriate cell labeling and tracking method
is essential for the development of cell-based therapeutic strategies.
Here, we are introducing a new method for cell labeling and tracking
by combining metabolic gylcoengineering and bioorthogonal copper-free
Click chemistry. First, chondrocytes were treated with tetraacetylated
N-azidoacetyl-d-mannosamine (Ac<sub>4</sub>ManNAz) to generate
unnatural azide groups (-N<sub>3</sub>) on the surface of the cells.
Subsequently, the unnatural azide groups on the cell surface were
specifically conjugated with near-infrared fluorescent (NIRF) dye-tagged
dibenzyl cyclooctyne (DBCO-650) through bioorthogonal copper-free
Click chemistry. Importantly, DBCO-650-labeled chondrocytes presented
strong NIRF signals with relatively low cytotoxicity and the amounts
of azide groups and DBCO-650 could be easily controlled by feeding
different amounts of Ac<sub>4</sub>ManNAz and DBCO-650 to the cell
culture system. For the <i>in vivo</i> cell tracking, DBCO-650-labeled
chondrocytes (1 × 10<sup>6</sup> cells) seeded on the 3D scaffold
were subcutaneously implanted into mice and the transplanted DBCO-650-labeled
chondrocytes could be effectively tracked in the prolonged time period
of 4 weeks using NIRF imaging technology. Furthermore, this new cell
labeling and tracking technology had minimal effect on cartilage formation <i>in vivo</i>