DNA Linking—Novel Chemistry
The use of DNA to link together dendrimers signifies the potential for developing highly specialized drug delivery systems. We continue to make significant progress in the development of a polyamidoamine (PAMAM) dendrimer-based drug delivery system to target cancer cells. A team of multidisciplinary scientists in M-NIMBS has proved that the nanometer-scale dendrimers have been engineered to be biologically functional, such as in targeting with cancer drugs (Methotrexate) cancer cells overexpressing receptors (folate or Her-2). But making these types of multifunctional nanoparticles is notoriously difficult and time-consuming, requiring months for each new molecule added to the dendrimer in sequential steps. Young Seon Choi, a Biomedical Engineering graduate student in collaboration with Dr. Thommey Thomas and Alina Kotlyar in the M-NIMBS, addressed this issue by designing nanoparticle clusters comprised of two different functional dendrimers, one for imaging and the other for targeting cancer cells. Young Seon Choi earned his Ph.D. degree in August 2005 and is now a Research Fellow at the University of Florida, Gainesville.
Each of the dendrimers also carried a single-stranded, non-coding DNA. These dangling lengths of DNA, typically 34-66 bases long, found complementary sequences on other dendrimers and knitted together, forming barbell-shaped, two-dendrimer complexes with folate on one end and fluorescence on the other end. With this approach, a library of single-functional dendrimers such as targets, drugs, and contrast agents can be synthesized in parallel, rather than sequentially, and then linked together in many different combinations with the DNA strands. In the future, this bi-functional dendrimer cluster system can be readily expanded or adapted to exploit various cancer-specific biomarkers. Having an array of single-functional dendrimers, such as targets, drugs, and contrast agents, and the ability to link them together quickly and easily in many different ways would enable a clinic to offer customized multifunctional nanomedicine based on this dendrimer cluster system.