Research is currently being conducted to study the use of serotonin-based nanoparticles in cancer therapy.
Further research suggests that using nanoparticles as delivery methods for chemo-therapeutic drugs such as Doxorubicin (DOX) is more advantageous to traditional chemotherapy. Nanoparticles exhibit photothermal (heating) effects when exposed to NIR (Near Infrared) light, which enhance its ability to deploy highly effective therapeutic agents more effectively and safely than current methods today.
Polydopamine (PDA) based nanoparticles have also been explored for biomedical applications. However, PDA has shown to be problematic during in vivo (into the body) administration because of its high nonspecific adhesive properties, which attracts potentially harmful blood proteins. Researchers have thus developed polyserotonin-based nanoparticles inspired by PDA to see how its performance compares.
The International Organization for Standardization (ISO) defines nanoparticles as ultrafine objects that are measurable in nanometers. There are three physical properties of nanoparticles: they are highly mobile in the free state, they have extensive specific surface areas, and they may exhibit quantum effects.
Quantum effects refers to the phenomenon in which several physical properties specific to the material, including melting point, fluorescence, electrical conductivity, and chemical reactivity are determined by the physical size of the nanoparticle itself.
Serotonin molecules undergo the process of autoxidation, or spontaneous oxidation at room temperature in the presence of oxygen in order to form similarly-sized nanoparticles in basic conditions. PDA monomers undergo a similar process, oxidized in solutions containing water, ethanol and ammonia at room temperature. Polyserotonin nanoparticle oxidation did not require a catalyst but had significantly lower rate of reaction compared to PDA oxidation. As a result, PDA nanoparticles are synthesized more quickly than polyserotonin nanoparticles, which is beneficial for chemotherapeutic drug production.
Nanoparticles combat against cancerous cells in two ways: they exhibit photothermal effects when exposed to radiation, and they release chemo-therapeutic drugs that are attached to its surface. The nanoparticles’ ability to release DOX is dependent on its adhesive properties and the formation of protein corona.
The photothermal effect (PTE) refers to the photoexcitation of electrons when the particle is exposed to NIR, Ultraviolet (UV) and visible radiation. Afterwards, the nanoparticles will release thermal energy, or heat, as the energized electrons attempt to restabilize. Photothermal effects work in conjunction with drug offloading to kill and suppress tumor cells.
Once administered, the nanoparticles circulate throughout the bloodstream and target tumor microenvironments, which are slightly more acidic relative to the blood (?). Polyserotonin nanoparticles were shown to release DOX much more efficiently in environments with a pH of 6.5 and 5.5, mimicking that of tumor and intracellular microenvironments. There are several factors that influence the overall behavior of the nanoparticles.
One of the biggest factors that determines the nanoparticles’ DOX-unloading capabilities as well as their overall biocompatibility during in vivo administration is their surface adhesive properties. Once the nanoparticles are administered into the bloodstream, external blood plasma proteins begin to “stick” to their surfaces, creating a shell-like structure called the protein corona. The proteins that attach to the surface influence the nanoparticles’ ability to circulate through the bloodstream and unload DOX. Results showed PDA adhesion force (~23 nanonewtons) was almost 4 times greater than that of polyserotonin (~ 6 nanonewtons). As a result, the total protein content is significantly larger on the PDA nanoparticles compared to polyserotonin, with 35% more plasma proteins found on its surface.
Protein coronas can have both positive and negative influences on the nanoparticles’ efficacy.
A coagulation (blood-thickening) protein known as Fibrinogen is a large protein found on the surfaces of both polyserotonin and PDA nanoparticles. Fibrinogen has shown to negatively affect nanoparticles, as its presence triggers the body’s immune system by stopping circulation of the blood (hemostasis) and releasing white blood cells (leukocytes).
In contrast, serum albumin, a protein produced in the liver responsible for maintaining fluid balance in the blood vessels, was also commonly found on the surface of the nanoparticles.
In contrast to Fibrinogen, Serum albumin has been shown to benefit the nanoparticles, reducing nonspecific adhesive properties of the nanoparticles, and allowing them to circulate in the blood for a longer period of time and thus release DOX into more tumorous microenvironments.
The efficacy of polyserotonin based nanoparticles is still unclear. While PDA-based nanoparticles exhibit higher levels of photothermal emission and synthesize at a faster rate, polyserotonin nanoparticles show lower levels of nonspecific adhesion and unload DOX particles more efficiently in acidic microenvironments.
Nanoparticles have the potential to become a more effective alternative to traditional chemotherapy for cancer treatment. Current treatment is limited due to the negative side effects that arise with each dosage. Traditional chemotherapy is unable to specifically target cancer cells, and consequently destroy healthy cells as well. However, nanoparticles have been shown to release chemotherapeutic drugs specifically in tumorous microenvironments that are slightly more acidic. Exposure to light will induce the photothermal effect and enhance the nanoparticles’ ability to unload chemotherapeutic particles.