DENDRIMER ARCHITECTURAL MODELING FOR THE NEW CANCER THERAPEUTIC APPLICATIONS

Carnegie-Mellon University, Pittsburgh PA

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Molecular Dynamics Simulation, dendrimer, cancer therapeutics, RNA interference Abstract: The University of Michigan Center for Biologic Nanotechnology (UMCBN) is developing new therapeutics for cancer based on dendritic polymer architecture. Current plan is to assemble functional dendrimers in a defined way to make a dendrimer cluster with multiple functionality. One unit can be a dendrimer with targeting moiety, a second unit a dendrimer with sensing, a third with imaging the tumor and a fourth with carrying and delivering the actual therapeutic. Then all units (shell) are attached to another dendrimer (core). In this manner, dendritic polymers can form complex structures that achieve all of the necessary therapeutic aspects against a cancer. Structural studies using MD simulations are crucial in achieving a multi-functional device from a dendrimer complex. We will predict the optimal parameters for a device and reduce considerable chemical bench work through these computational studies. In addition to cancer therapy, dendrimers have been proved to be used as excellent gene delivery vehicles. We will use dendrimer as a potential RNA interference delivery system. Once the efficacy is proved, this new type of RNA interference can be occurred as cell or organ specific manner. We will perform MD simulations among oligonucleotides and dendrimers to find optimal conditions for this task. Sequence specificities and thermodynamic parameters of oligonucleotides targeting certain genes will also be calculated using our own algorithms. Target genes will be depression related genes in addition to cancer related ones.