Marium's Research Blog
Tripeptide Stabilized Nanoemulsions for Cancer Therapy
A carboplatin derivative consisting of two oleic acids attached to a platinum head, used to kill cancer cells, was investigated in this project through chemical simulation software. One of the challenges of this class of anticancerous drugs is its high level of toxicity to the human body, which results in low clinical dosings of the drug and ultimately ineffective therapy. Thus, for drug delivery to the human body, the carboplatin derivative requires an emulsifier to stabilize it and shield its toxic agents. The emulsifiers used in this project are tripeptides because of their biodegradability and it has been shown that they are promising self assembly candidates in a previous study. In the first phase of this project, general features of oleic acid aggregates in water solution are investigated. In the second, tripeptides, specifically KYF (Lysine- Tyrosine - Phenylalanine) and DFF (Aspartic Acid- Diphenylalanine), are added to these aggregates in order to study the tripeptide stabilized nanoemulsions. The simulations gave insight about the interactions present in the nanoemulsions.
Below is a report discussing the findings of the Spring 2018 semester's research.
Currently, further work is being conducted to collect quantitave data using dynamic light spectroscopy (DLS) to supplement the results found through molecular modeling and investigate the effects of pH.
Due to limitations of the chemical simulation program, the platinum head of the carboplatin derivative was replaced with a carbon atom. Thus, the two oleic acid chains were bonded by a carbon atom instead of platinum. These generated molecules aggregated by assembling as a bilayer. This assembly was very different when compared to the aggregation of single chains of oleic acid. In conjunction with this simulation, a KYF-Oleic acid nanoparticle was synthesized in the lab. An ideal nanoparticle is 100-280 nm in its effective diameter when measured by DLS. A challenge in the synthesis of these nanoparticles is that they precipitate if not completely stable, however, after several trials an ideal method was established. The next step is to investigate how the size and zeta potential of the nanoparticle changes as a function of pH. It is hypothesized that as the pH surrounding the nanoparticles increases, the size of the nanoparticle will decrease. The excess base will consume the oleic acid on the surface of the particle, making the surface negatively charged. It is expected that the increasing number of ions in the nanoparticle will cause the particle to split and ultimately alter the average size of the nanoparticles in solution.
Zeta potential is particulary important because it affects the drug's interactions with surrounding cells in the human body. A nanoparticle with a postive zeta potential is more likely to react with blood components and increase in size. By increasing in size, the nanoparticle will not be able to penetrate cancer cells. The proposed mechanism that the carboplatin drug takes is the release of the Platinum head upon hydrolization in the body. Thus, by also investigating how properties of a KYF-Pt-Oleic acid nanoparticle change as a function of pH, it is possible to gain insight about the mechanism when compared to the properties of the perviously mentioned KYF-Oleic acid nanoparticle.