|REU student Jashaun Bottoms (left) with faculty mentor Chemistry and Biochemistry Professor Marie Christine Daniel Onuta (right) in Prof. Daniel Onuta’s nanoparticle synthesis laboratory.|
This summer I am conducting research in the laboratory of Prof. Marie Christine Daniel Onuta in the Department of Chemistry and Biochemistry of the University of Maryland Baltimore County (UMBC) in the area of nanotechnology-based drug delivery. Realizing efficient drug delivery is one of the grand challenges facing cancer treatment nowadays. There are many drugs that have proven effective in fighting cancer, but when these drugs become active in parts of the body other than the tumor, they are highly toxic. This toxicity often results in severe side effects and ineffective treatment. There is need for a drug delivery system that is more specific in targeting only cancerous cells. Noble metal nanoparticles have surfaced as a possible drug delivery system that can do just that.
Nanoparticles have the potential to improve the transport and effectiveness of cancer drugs, as their size affects how a drug is distributed throughout the body and delivered to a tumor site. If the nanoparticles are too small or too large, they will be cleared through the kidneys or liver, respectively, but when the nanoparticles are just the right size, they circulate in the body longer allowing for maximal tumor uptake. Their size also aids in targeting tumors through the enhanced permeability and retention effect, which allows the nanoparticles to accumulate in tumor tissue as opposed to normal tissue, reducing the toxicity of the drug. Nanoparticles also have a high surface-to-volume ratio, which means that they can be loaded with more drug molecules to allow for a higher dosage. More so, the nanoparticles can be designed into multifunctional drug delivery systems. This multifunctionality is achieved by decorating the nanoparticles with tree-like molecules called dendrons (Fig. 1A). The dendrons are monodisperse and serve as “backbone” molecules. The dendrons can be terminated with different chemotherapeutic drugs, imaging dyes, and targeting agents and then combined around a central nanoparticle to form a multifunctional dendrimer (Fig. 1B).
This project involves making gold nanoparticle-cored dendrimers and terminating them with the chemotherapeutic agent cisplatin. To do so, poly(propyleneimine) dendrons are first synthesized in a divergent method. The dendrons are then attached to tetraethylene glycol (TEG) spacers, which help to reduce steric hindrance when coupling the bulky dendrons with the gold nanoparticles (GNPs). The TEG spacers are terminated with thioctic acid, giving the molecule a cyclic disulfide group as its focal point for attachment onto the gold core. These two sulfur atoms are what create stronger bonds with the GNP core, making the dendrimer more stable. Once the spacers and dendrons are coupled, the cisplatin drug molecules are added to the ends of the dendrons through a cleavable bond to allow for specific release. The completed dendrons are then attached to the GNPs to create the dendrimers.