Nanoparticles: The All-in-one Package of Cancer Treatment

Nanomedicine aims to combine both diagnostic and therapeutic methods into a single,
integrated approach. The article A Nanostrategy for Efficient Imaging-Guided Antitumor
Therapy through a Stimuli-Response Branched Polymeric Prodrug by Cai et al., 2020, proposes
a new antitumor treatment for breast cancer. This new treatment is a polymer that clumps
together to form a nanoparticle that contains several different molecules. The nanoparticle not
only treats cancer cells, but also allows imaging and drug monitoring, marking a major
advancement in cancer therapies.

The components making this possible are a biodegradable outer shell, drug core, imaging
agent, and trigger mechanism. The outer layer is made from a polymer, a long chain of
molecules, which protect the drug core. At the core of the polymer is paclitaxel (PTX), an
anti-cancer drug known to stop cancer cells from growing. Attached to the polymer are imaging
agents that allow to track the location, release, and amount of drug delivered to the tumor. All
these components are released using a trigger mechanism designed to break open in specific
conditions. Ultimately, this drug works as a GPS-guided delivery truck that carries a package of
anti-cancer medicine and imaging agents to the correct location, breast cancer cells.
The nanoparticles flow through a person’s body via three different pathways:

“clathrin-mediated endocytosis”, “caveolin-mediated endocytosis”, and “macropinocytosis”.
Clathrin-mediated endocytosis describes when the nanoparticles are absorbed from the cell
surface to the cytoplasm with the help of transport vesicles. Caveolin-mediated endocytosis is
similar to clathrin-mediated endocytosis, but the nanoparticles are moved through the cell
membrane through bulb-shaped pouches called caveolae. Macropinocytosis is where cells take
these nanoparticles to the cytoplasm through large amounts of fluid.

After the nanoparticles enter the body, they spread to the lysosomes, where they release
the anticancer drug PTX, and then to the other parts of the cell. PTX works by stabilizing
microtubules and preventing them from breaking down, which stops cell division and causes cell
death, otherwise known as apoptosis. Microtubules are essential for cell division, so stabilizing
them prevents them functioning normally. In addition to affecting microtubules, the nanoparticles
also lower the amount of the specific protein that prevents cell death and increase the amount of
the proteins that promote apoptosis.

One of the two imaging methods used in this study was MRI, which was performed with
the help of an MRI contrasting agent called Gd(III). Tracking Gd(III) levels led to the discovery
that the nanoparticles linger in blood circulation for a prolonged period, which helps with
imaging and treatment. The longer the nanoparticles linger in the bloodstream, the more time is
given for them to reach the tumor. The amount of Gd(III) in the body also significantly decreases
after 120 hours, suggesting that the nanoparticles eventually slowly leave the body. This means
that they are likely safe and biodegradable.

Other than MRIs, fluorescence was the second method of imaging used in this study.
Cyanine 5.5 was the fluorescence dye used to image and track the nanoparticles. It was
discovered that after 6 hours, the fluorescence in the tumor was so strong when tracked that it
was hard to distinguish between blood vessels and the tissue around. This indicates that there
was an accumulation of the nanoparticles in the tumor, which proves that the nanoparticles are
highly effective in reaching the tumor. One key finding from the fluorescence imaging was that
the most nanoparticles were found at the site of the tumor at 24 hours.

The molecules used in the anti-tumor medical treatment have many beneficial properties
for its patients. For example, the pHPMA-drugs have special medicinal properties that dissolve
in water, last longer in the body and are more effective against tumors while causing less harm.
They break down into smaller fragments inside tumors which help the body get rid of the carrier
more easily and lowers the risk of it causing other issues. This medicine uses a special type of
polymer that breaks down safely in the body and can be mixed with other cancer drugs which
can be easily made to have unique features that help target tumors more effectively. Combining
the MRI and fluorescence imaging helps track how well the medicines work by measuring
volume changes and providing real-time updates on treatment efficacy.

In particular, the anticancer drug PTX are tiny nanoparticles designed to remain in the
body longer and specifically target tumors, minimizing impact on other organs like the liver and
kidneys. After researchers conducted their experiment which resulted in a 93% tumor growth
inhibition and where four out of seven tumors were eliminated, they concluded that this new
system worked much better at stopping tumor growth and even eradicating some tumors
completely. This is most likely due to better molecular structure, more effective targeting of
tumors, and faster drug release triggered by enzymes. Overall, the PTX nanoparticles circulate in
the body for a longer period of time and target tumor sites effectively as shown by the
pharmacokinetic studies, MRI and fluorescence imaging. These findings highlight the
nanoparticles potential as a versatile and effective treatment for various cancers by continuing to
be safe for healthy tissues and organs.

There are some interesting facts about the treatment such as the anti-tumor drug getting
released only when the nanoparticle detects the presence of a tumor. It detects the presence of
tumor by high acidic pH or other distinctive ways and gets released. Since it is being directly
released in the presence of a tumor and not everywhere in the body, the drug has less resistance.
Another one is that nanoparticles can easily get inside the tumor thus improving the infiltration
and the branched polymer provides better stability and doesn’t degrade much and the structure
can carry multiple things such as imaging properties and anti-tumor drugs. Since the technology
has imaging properties, the real time feedback or the location and situation of the tumor is
detectable. This technology has the potential to be used for more. Such as to detect infection or
inflammation in the body and so on.