Synergistic anticancer therapy with two cell killer agent systems in one nanocapsule
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In their quest to destroy cancer cells, researchers are turning to
combinational therapies more and more. Scientists from Germany and China
have now combined a chemotherapeutic and photodynamic approach. All
agents are encapsulated in nanocapsules with a protein shell to be
delivered to the tumor. There, light irradiation triggers a cascade of
events, which lead to the destruction of the tumor cells, the
researchers write in the journal Angewandte Chemie.
Different anticancer agents use different strategies. DNA-damaging
agents make the DNA dysfunctional so the tumor cannot grow. Photodynamic
agents generate reactive oxygen species (ROS) when irradiated with
light. These ROS then interfere with organelles in the cell and push the
cells toward programmed cell death known as apoptosis.
However, some cancer types have developed resistances. Either the
drug cannot enter the cell or the cells quickly repair the damaged DNA
strands. To enhance effectivity, Katharina Landfester and her colleagues
from the Max Planck Institute for Polymer Research, Mainz, Germany, and
researchers from Dalian University of Technology, Dalian, China,
combined chemotherapeutic and photodynamic agents. All agents were
packed inside a nanocapsule for delivery to the tumor cells.
Photodynamic therapy can be less effective in solid tumors within
which the oxygen level is too low to generate enough ROS. Therefore, the
scientists used a modified system that partly recycles oxygen. In this
system, a photosensitizer produces ROS after light irradiation. Enzymes
of the cell convert the ROS to hydrogen peroxide. Another reagent called
Fenton reagent—which is basically iron in its highest oxidation
state—then back-transforms the hydrogen peroxide to ROS and oxygen.
The authors said that it was challenging to assemble all reagents in
one nanocapsule. The chemotherapeutic agent, cisplatin, is poorly
soluble in water, while ovalbumin, the nanocapsule protein, does not
dissolve in the organic solvent. Using a miniemulsion technique, the
scientists eventually combined all three reagents in a solvent mixture
and wrapped them up in a shell of ovalbumin. They stabilized and
emulsified these nanocapsules by adding a copolymer based on
poly(ethylene glycol).
The scientists tested this system on tumor cell lines. The
nanocapsules entered the cells, released their loads, and developed ROS
when irradiated with red light. The agent set also killed cells that
were resistant to cisplatin or had a particularly low oxygen
concentration.
The combined encapsulated drugs also stopped tumor growth in live
mice. The authors found that the reagents accumulated in the tumor
tissue. They also made the tumors shrink over time without affecting
healthy tissue or other organs.
The authors highlighted that the anticancer agents were delivered to
the tumor in nanocapsules and worked synergistically. Treatments
involving only one agent, or a combination of two, were much less
effective. The authors proposed that similar synergistic platforms will
play a major role in future therapy settings.
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About the Author
Professor Katharina
Landfester is a director of the Max Planck Institute for Polymer
Research in Mainz, Germany. Her research interest is in the creation of
colloids with increasingly specific and complex properties for new
materials and biomedical applications. The nanocarrier research group
focuses on translating drug nanocarriers into clinically relevant
applications with the aim to reduce dosages and increase target
specificity.
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Contact: Katharina Landfester, Max-Planck-Institut für Polymerforschung (Germany)
Registered journalists may download the original article here:
Synergistic Anticancer Therapy by Ovalbumin Encapsulation-Enabled Tandem Reactive Oxygen Species Generation