Session 8, Abstract 48
MODIFICATION TO BACTERIOPHAGE LAMBDA PROCAPSIDS TO CREATE A TARGETED THERAPEUTIC DELIVERY SYSTEM
Justin Morin*, Madyson Ziegler*, Kyle Koshland and Breanna Perez (Kristopher J. Koudelka), Dept. of Biology, Point Loma Nazarene University, 3900 Lomaland Dr., San Diego CA 92106
Current cancer treatments, like chemotherapy, are designed to attack rapidly dividing cells. The efficacy of this style of treatment is significantly reduced as chemotherapeutic drugs are delivered to all tissues thus reducing the amount of drug that reaches the site of disease while creating harmful side effects in other healthy, rapidly dividing cells. Using bacteriophage lambda procapsids, we aim to develop a form of drug delivery that more specifically targets diseased sites and that decreases the dosage of chemotherapeutic drugs used. Our research involved the modification of the bacteriophage lambda procapsid via electrophilic addition and nucleophilic acyl substitution. Transferrin (TF) was chosen as a targeting ligand to increase binding affinity to cancerous sites because cancer cells are known to upregulate TF receptors. TF was attached to cysteine or lysine residues on the procapsid exterior using functionalized polyethylene glycol (PEG) linkers. The PEG linker was added to decrease the immunogenicity of the lambda procapsid by blocking physical antibody and immune cell access to the protein-based procapsid. We successfully modified TF protein with both dye and a PEG linker, procapsids with two separate dyes, and a procapsid with dye and a PEG-TF-dye complex. Modifications were confirmed using fast protein liquid chromatography (FPLC) and spectrophotometry. In the future, in vitro as well as in vivo uptake into cancerous cells will test whether this complex achieves greater specificity as well as increased reduction of cancerous cells when drug loaded.