Gold Nanoparticle-cored Dendrimers as Multifunctional Drug Delivery System for Chemotherapy

Graduate #40
Discipline: Chemistry and Chemical Sciences
Subcategory: Chemistry (not Biochemistry)

Jashaun Bottoms - Western Michigan University
Co-Author(s): Arunendra Saha Ray and Marie-Christine Daniel, University of Maryland, Baltimore County, Baltimore, MD

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Chemotherapy is administered in a manner that is not tumor-specific, and the drugs are generally distributed throughout the body. When the drugs become active in parts of the body other than the tumor, they are highly toxic, causing severe side effects. Gold nanoparticles have the potential to improve the transport and effectiveness of chemotherapeutic agents because their size aids in targeting tumors through the enhanced permeability and retention effect. The nanoparticles can also be designed for multiple functions by decorating them with tree-like molecules called dendrons and terminating the dendrons with different chemotherapeutic drugs, imaging dyes, and targeting agents. The dendrons can then combined around a central gold nanoparticle to form a multifunctional dendrimer. In this project, second-generation poly(propyleneimine) dendron was synthesized and attached to a tetraethylene glycol spacer terminated with thioctic acid. The thioctic acid molecule contains a cyclic disulfide group that is known to infer strong attachment onto the gold core. Once the spacer and dendron were coupled, the dendron was grown to third-generation (8 branches) and its termini were modified so that cisplatin drug molecules could be attached through a cleavable bond (acyl hydrazone) to allow for specific release into cancer cells. All intermediates were characterized using 1H NMR spectroscopy (for the dendron) or mass spectrometry (for the cisplatin derivatives). The final product was characterized by NMR, thermogravimetric analysis and ICP-MS. Future studies will include attaching the cisplatin-terminated dendrons to gold nanoparticles.

Funder Acknowledgement(s): The project is supported by the National Science Foundation Research Experience for Undergraduates (REU) Award No. CHE-1460653.

Faculty Advisor: Marie-Christine Daniel, mdaniel@umbc.edu

Role: For this project, I synthesized the dendron and spacer molecules, and I coupled them together. I then attached the cancer drug cisplatin to the end of dendrons. Not only was I responsible for synthesis, I also characterized the products using thin layer chromatography and nuclear magnetic resonance spectroscopy.