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Name(s): Nevin Daniel High School(s): Ward Melville High School, East Setauket, NY Mentor: Dr. Iwao Ojima Project Title: Novel Asymmetrical Bow-Tie PAMAM Dendrimer Conjugates as Model Systems for Anticancer Taxoid Drug Delivery.
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High School(s): Ward Melville High School, East Setauket, NY
Mentor: Dr. Iwao Ojima
Project Title: Novel Asymmetrical Bow-Tie PAMAM Dendrimer Conjugates as Model Systems for Anticancer Taxoid Drug Delivery
An optimal anticancer chemotherapeutic agent should not only have an effective drug, but also a biocompatible drug delivery vehicle that aids with drug solubility and increases plasma circulation time to passively target cancer cells, a mechanism for controlled drug release, and a targeting moiety that serves to actively target cancer cells. This study worked toward the development of such an agent by designing and synthesizing novel asymmetrical bow-tie PAMAM dendrimer conjugates that can act as model systems for effective anticancer taxoid drug delivery by combining an effective, active tumor-targeting module for specificity; a dendrimer scaffold composed of a two half-dendrons of distinct Generation, covalently linked with a bis(maleimido)alkane core, for enhanced circulation time and passive targeting via the Enhanced Permeability and Retention effect; a self-immolative disulfide linker that allows for controlled release of the drug within the cell; and a large payload of second-generation taxoid that acts as an effective anticancer drug. With good yields for a number of novel reactions, two conjugates were successfully synthesized and characterized: a fluorescent probe conjugate to be used for future internalization studies and a second-generation taxoid conjugate to be used in future cytotoxicity assays. Such conjugates are the first in their class of dendrimer conjugates and, with further chemical modulation and biological assessment, present impressive potential to give rise to revolutionary new materials in the field of anticancer drug delivery.