Design and synthesis of therapeutic agents: From small molecules to polymeric nanomaterials

Novel approaches are needed to address the limitations of traditional therapy methods that are in practice today, for improved treatment of diseases. This thesis evaluates such approaches through the development of new molecular and materials-based systems. The first part of this thesis focuses on the synthesis of a prodrug molecule for pancreatic cancer treatment while the second part includes polymeric nanomaterial-containing delivery systems for biological applications. In the first part, two synthetic pathways were investigated to synthesize a prodrug system comprised of gemcitabine, a chemotherapy agent, and hydroxychloroquine which is known to eradicate pancreatic cancer stem cells. Products linked with acid-sensitive linkages with and without disulfide bonds between them were synthesized, and evaluated for their in vitro cytotoxicity against the Bx-PC3 cell line. Another approach to specifically deliver drugs involves the utilization of localized delivery systems. In this regard, in the second part of this thesis, polymeric nanomaterials were evaluated as drug delivery platforms. As nanomaterials, carbon nanotubes (CNTs), magnetic iron-oxide nanoparticles (IONPs) and reduced graphene oxides (rGOs) were utilized in four distinct projects. CNTs wrapped with a reactive polymer using physical interactions were fabricated, and evaluated for attachment of bioactive molecules using the thiol-maleimide reaction. In another project, rGO-embedded photothermal hydrogels were synthesized using a thiol-ene reaction and were evaluated for on-demand active release using near-infrared (NIR) light to release antibacterial agents inside the hydrogel. In the last two projects, IONPs were coated with two different polymers using reversible addition-fragmentation chain transfer (RAFT) polymerization and these constructs were used to design different drug delivery and release systems. While one polymer contains furan groups on the side chains, the second polymer includes maleimide units for the post-polymerization functionalization of the surface. Overall, this thesis puts forth new drug delivery platforms that may find therapeutic applications.