20,000 unnecessary deaths from Lymphoma each year in America alone, 300,000 unnecessary death worldwide with no real and effective solution to prevent it from happening? It is crazy to think such drastic effects are caused by just one cancer. Is there a viable solution that can prevent such death from happening?

Lymphoma

So, what is Lymphoma? Well, lymphoma is a cancer that starts in the lymph system that have two main types: Hodgkin Lymphoma and non-Hodgkin lymphoma. Non-Hodgkin lymphoma is a an unpredictable cancer that can appear in any lymph nodes in the body while Hodgkin Lymphoma is more predictable and happens in the upper body like the neck and chest.

Lymphoma is a horrible cancer because it makes us more susceptible to infection and diseases such as heart disease as lymphocytes or lymph nodes control immune response or produce killer T-Cells.

Cancerous lymph cells multiply uncontrollably just like any other tumor, but in the case of lymphocytes this creates an inability for the body to fight infections with healthy T-cells — so the treatment process becomes counterintuitive since chemotherapy is meant to reduce this multiplication effect, but if the body isnt able to adjust to unhealthy lymph tissue, its a lose lose situation

PDTs

Photodynamic therapy (PDT) is a method used to eradicate cancerous cells by using drugs that is activiated by light as a or a laser such as LEDs are known as photosensitizers to kill cancerous cells.

Cells would essentially have absorbed photosensitizers that would be set to a specific wavelength of light which would then produce “oxygen radical” that would begin to kill off the cells.

The drug would injested from the mouth, spread on the skin, or given through an IV, depending on where the tumor is in the body. Most of the drugs would leave normal cells after 1–3 days but remain in pre-cancer or cancerous cells which would then be exposed to the photosensitizer.

Depending what type of cancer it is will be shown to direct the light like for skin cancer, the light would be directed towards the direct center. It would then create that form of oxygen that kills cells

Huge Drawbacks:

Photosensitizers in photodynamic therapy cannot pass through more than 1/3-inch of tissue. So, photodynamic therapy can only be used to treat tumors that are on or “just under the skin or on the lining of internal organs or cavities” (National Cancer Insititute).

Furthermore, many side effects occur from PDT such as burns, pain, swelling are all possible even when PDT is very limited. Other side effects include:

• Painful breathing

• Shortness of breath

• Eye Irritation and redness

• Skin irritation and becoming more susceptible.

Benefits:

It is much more precise than many other cancer method and prevents much killing of healthy cells like chemotherpay does. However, it not reaching the needed areas ( more effective with precision but not so much as being effective to kill the tumor itself unless small).

What are Researchers doing Today?

Newer delivery of photosensitizers that allows for more precision with an immune response that directs the immune system into eradicating the tumor known as photoimmunotherapy or PIT. An immune protein is combined with a photosensitizer

Researchers are also developing a new type of PDT called photoimmunotherapy, or PIT. In this treatment, a photosensitizer is combined with an immune protein that delivers the photosynthesizer to cancer cells. When light is applied, the photosynthesizer kills the cancer cells. This process also causes an immune response inside the tumor that can cause more cancer cells to die. “

This new immune response allows for deeper and larger tumors to be accessed while being even ore precise and more powerful against those tumors

However, in Lymphoma cancer, there is already a weak immune response to begin with, preventing any photoimmunetherapy to effectively get rid of the virus, rendering this amazing solution into uselessness.

New Solution: UCNPs

Up-conversion nanoparticles (UCNP) has been a new recent development where these nanoparticles are able to used near-infrared (NIR) light that activates UCNPs to emit high-energy light (commonly UV light) that activates the surrounding photosensitizers.

These photosensitizers would then make singlet oxygen and other reactant oxygen species (ROS) which would kill of the designated areas that is involved.

This NIR with UCNPs allows for scientists to be able to lessen the side effects and become more effective by being able to penetrate up to 3x more than a regular UV light that would be used in regular PDT treatment as well as lower the phototoxcity that was inflicted in nearby normal cells and tissue that other method like chemotherapy would have infected.

How would this all work?

UCNPs as energy donors will have to first be loaded onto the photosensitizer (PS) molecules for light having energy from donor to acceptor in NIR- induced PDT.

Silica Encapsulation is one of the most effective methods that are used to load UCNPs on PS molecules by coating UCNPs with a silica shell.

For example, a group of researchers had developed NAYF4 UCNP carriers for zinc(II)-phtalocyanine (ZnPc). Through physical absorption, the ZnPc was encapsulated after the UCNP was encapsulated, creating a stable and airtight encapsulation. Finally, under a 980-nm NIR light, nanoparticles were excited to create singlet oxygen that would destroy the cancer cells.

After loaded with the ZnPc molecules, the 980-nm NIR light would then activate the ZnPc molecules through an energy transfer from the UCNPs as it would emit the visible light needed because of the NIR light.

This posed a problem as an experiment with this was conducted, but it created singlet oxygen that would attack DNA bases and mitochondria in our cells during the 5 minute NIR irraidation time and the laser going at 0.5 W. However, Shan et al. have done a study that had increased the ratio of photosensitizers that were loaded on the UCNPs that had made up 10% of the total weight while encapsulating 100nm of UCNPs and using meso-tetraphenyl porphine photosensitizers that allowed much DNA and mitochondria from being killed. Through this newly set up experiment, Shan, a photodynamic researcher, along with many of his peers, had used “980-nm NIR light excitation at 134 W/cm2 for 45 min,” effectively killing the cancerous cells (Shan et al.).

Using these new photosensitizers and varying the ratio size, Shan was able to avoid creating such dangerous singlet oxygen that ZnPc was producing and lessening the amount of PS molecules compared to the UCNPs. These researchers concluded that NIR excitation with a UCNP-PS nanocomplex offered a incredibly productive way to kill off cancerous cells.

To further enhance tissue penetration, a Ce6 solution was created in recent nanomedicine studies that would combine with UCNPs. Using pork tissue to test it’s effectiveness, a UCNP with a Ce6 sample was ineffective to penetrate even 3mm of pork tissue; however, with the addition of the 980-nm light, it created significant amount of oxygen production even when it was blocked with an 8mm pork tissue.

However, even though 980-nm NIR light is the most effective excitation as it offers effective tissue penetration to the extent of 3.2cm, it causes skin heating that could damage nearby tissues as water absorption’s peak is 980- nm. 915-nm NIR light acts just like 980-nm NIR light and offers a deeper tissue penetration. (Zhan et al). and avoid such skin heating to occur in UCNP-based imaging and PDT treatment.

While UCNPs work in PDT, many imaging software are used in order to follow these particles and image tumors such as UCL imaging, so not only does UCNPs have the potential of eradicating tumors but also offers the opportunity to at least image the tumor to determine the extent of the tumor.

How would the UCNPs be Delivered?

This nanobot has three wheels, two lined with motors (shown with the metal plates) while the third wheel (the one across from the coil) acts as a stabilizer wheel to prevent the machine to tip over.

The top dome to where this structure meets the cylinder (signified by the line) displays the payload, carrying the necessary UNCPs that have the photosensitizers to eradicate the tumor.

As you can see, there is a hole on the bottom of this machine. With a pipe of metal running from the payload to this hole, these UCNPs will be able to be directly deployed on these tumors caused by Lymphoma anywhere in the body.

The payload will be equipped with an automated seal in order to prevent any UCNPs from getting out of the pipe too early from the cancerous site.

Finally, the coil will be used as self-propelled particles called “nanoswimmers” discovered by researchers from the University of Colorado Boulder. These coiled structures have already been tests by these researchers that prove its effectiveness in the overall environment of the body.

This nanocarrier can totally revolutionize the deployment of UCNPs to specific tumor sites and allows

Is it Possible in the Future?

The only concern about this solution is the nanotoxcity that can occur in our bodies; however, many scientists are developing new ways with biocompatible coatings that would be used in UCNPs, and with the recent development of nanomaterials, researchers are confident to be able to develop such substances in just a few years!

Our solution is easy to do as it has already been tested and trialed before while achieving the ultimate effectiveness that is needed in order to offer a deep penetration of tissue while limiting the pernicious effects of these methods.

Ce6 solution, NIR light set to 915-nm NIR, meso-tetraphenyl porphine photosensitizers, and UCNPs with silica encapsulation are all components in our model to create a solution to Lymphoma.

Works Cited:

National Library of Medicine. (2013). Upconversion nanoparticles for Photodynamic therapy and other cancer therapeutics. PubMed Central (PMC). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3645058/#B44

Shan JN, Budijono SJ, Hu GH, Yao N, Kang YB, Ju YG. et al. Pegylated Composite Nanoparticles Containing Upconverting Phosphors and meso-Tetraphenyl porphine (TPP) for Photodynamic Therapy. Adv Funct Mater. 2011;21:2488–95.

Zhan QQ, Qian J, Liang HJ, Somesfalean G, Wang D, He SL. et al. Using 915 nm Laser Excited Tm3+/Er3+/Ho3+-Doped NaYbF4 Upconversion Nanoparticles for in Vitro and Deeper in Vivo Bioimaging without Overheating Irradiation. Acs Nano. 2011;5:3744–57.

You Exec. “The future of “nanobots” in 2023 and beyond.” YouTube, 2023, www.youtube.com/watch?v=oFH3gFFV0AI&t=462s. Accessed 21 Apr. 2024.