Radiotherapyis one of the most prevalent methods for cancer treatment. However, a challenge
for cancer radiotherapy is that therapeutic doses used can damage neighboring
normal cells. This paper describes a new method to enhance radiation therapy by
delivering gold nanoparticles into cancer cells, where gold nanoparticles were
modified with virus-derived cell penetrating peptides (CPPs) and Poly (Ethylene
Glycol) (PEG). PEG was used to improve nanoparticles blood circulation time,
and CPPs were used to enhance internalization of the nanoparticles into cells.
The internalization of CPP-PEG modified gold nanoparticles in cancer cells
(HeLa cells) was confirmed with differential interference contrast imaging. A
variety of assays (such as bright field imaging, MTT, DNA damage, reactive
oxygen species and immunofluorescence) were used to detect cellular and genetic
damage in cancer cells. We found that CPP-PEG modified gold nanoparticles
caused more cellular and DNA damage than gold nanoparticles at the same radiation
doses due to enhanced generation of free radicals. In contrast, damage was not
severe for normal fibroblasts cells under the same conditions. This method can
potentially be used to severely damage DNA and other cellular structures of
cancer cells, while minimizing damage to normal cells during radiation therapy.
Currently, chemotherapy, surgery and radiotherapy are the most
effective methods to treat cancer. Radiotherapy targets and destroys tumor
with ionizing radiation. The laser generates free radicals that damage various
cellular components including DNA. One of the advantages of using radiotherapy
is that it can kill tumor even though they are intermix with normal healthy
tissue. Hence, more than 50% of cancer patients received radiotherapy
treatment. However, the therapeutic doses used during radiotherapy can damage
nearby normal cells. Various chemicals and nanoparticles were tested to
act as radiosensitlzers to enhance radiotherapy.
Despite its essential role in maintaining cell function, cell
membranes present a major barrier for intra-cellular delivery of therapeutic
nanoparticles. Hence, even though ions or nanoparticles of high atomic
number elements (such as gold, platinum and bismuth) have been used to enhance
radiation therapy by absorbing ionizing radiation and generating free radicals
at high yield, the measured enhancement effect due to nanoparticles has
been negligible, likely because inefficient nanoparticles were present in
cancer cells and X-ray generated free radicals cannot reach the vicinity of DNA
to cause damage
Nanoparticles can be modified to have desirable surface
properties to allow for uptake and targeted delivery into cells and subcellular
locations. Non-viral vectors such as amino-modified silica
nanoparticles, iron oxide nanoparticles, carbon nanotubes and gold
nanoparticles have been used to deliver nucleic acids in transfection assays. In particular, gold (Au) nanoparticles are stable, non-toxic and easy
for surface modification, making them a suitable candidate to deliver molecules
into cells. However, to reach their full potential in cellular
applications such as radiotherapy, robust methods must be developed to allow
for the controlled uptake of gold nanoparticles into cells. This requires the
gold nanoparticles to be functionalized with engineered coatings to promote
their cellular uptake and targeted delivery.
Poly ethylene glycol (PEG) was used to coat nanoparticles to
improve their blood circulation. However, PEG interactions with cell
surface ligands prevent nanoparticles intra-cellular uptake. One solution to
use cell penetrating peptides (CPPs). CPPs are relatively short cationic and/or
amphipathic peptides and are efficient cellular delivery vectors due to their
intrinsic ability to enter cells and mediate uptake of a wide range of
macromolecular cargo. The various molecular cargo delivered by CPPs ranges
from nanosize particles to small chemical molecules and large fragments of DNA.
The “cargo” is associated with the peptides either through chemical linkage via
covalent bonds or through non-covalent interactions [26]. The function of the
CPPs is to deliver the cargo into cells, a process that commonly occurs through
endocytosis with the cargo delivered to the endosomes of living mammalian cells.
No comments:
Post a Comment