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  • Undergraduate Poster Abstracts
  • ap075 SUPER LIPOSOMES: TARGETED COMBINATION THERAPIES FOR INDUCING CELL DEATH IN CANCER CELLS

    • Magaly Salinas ;
    • George R. Negrete ;

    n/a

    SUPER LIPOSOMES: TARGETED COMBINATION THERAPIES FOR INDUCING CELL DEATH IN CANCER CELLS

    Magaly Salinas, George R. Negrete.

    The University of Texas at San Antonio, San Antonio, TX.

    A cysteine-derived acrylamide platform was envisaged as a chemical core to which lipid and peptide ligands or reporter groups could be readily attached in a highly modular process. The L-cysteine-derived core supports carboxylic acid, aryl nitro, and acryloyl substituents. A thiol lipid module was conjugated to the thiazolidine acrylamide, and the nitro group was reduced to the corresponding amine to generate a novel cysteine lipid analogue (CLA). Fmoc protection generates a construct that functions as a component in solid-phase peptide synthesis (SPPS) of lipopeptides such as EPDIM-CLA. The EPDIM sequence, known for binding to α3β1 integrin receptors and inducing apoptosis in cancer cells, serves a dual function as a targeting ligand and as a therapeutic agent. The synthesized EPDIM-CLA lipopeptide will be incorporated into PEGylated liposomal doxorubicin formulation (DOXIL®) to demonstrate that 1) the targeting lipopeptide attaches to the surface of DOXIL®, 2) enables binding of the targeting liposome to cancer cells, and 3) the targeted liposomes promote cell death in cancer cells. In future work, this multi-component system can be tailored to incorporate any targeting lipopeptide or drug-releasing ligand while encapsulating a chemotherapeutic drug, such as doxorubicin, in a liposomal formulation yielding a “super liposome” for targeted combination therapies. [Support for this research was provided by NIGMS RISE GM060655.]