The construction of plasimid vector encoding polypeptide for drug delivery to cancerous tissue. (Celluar, Molecular and Developmental Biology).

Soumo De, St. Andrews Episcopal Middle School, Ridgeland, MS 39157

Nonspecific action of chemotherapcutic drugs limit therapeutic effect in tumors. Other approaches such as surgery and radiotherapy also have limitations in treatment of cancer. Here, we have taken a targeted approach for delivery of the drug to tumor cells where the drug will be linked to a defined polypeptide carrier (Elastin like peptide, ELP) which have the property of physical phase transition at an elevated temperature (Tt). This would allow to selectively accumulate the drug-polypeptide complex in tumor tissue under localized hyperthamic conditions. Following entry into cells the drug (oligodeoxynucleotide) will bind to the corresponding cancer causing message rnolecule to stop its signal for unregulated tumor growth. To achieve this objective a plasmid construct was made consisting of ELP codon sequence ligated to polylysine codon AT one end and a tripeptide (RGD) codon at the other end. After expression in a host cell polylysine (positively charged moeity) would attract the negatively charged drug, a n oligodeoxynucleotide, to bind by electrostatic interaction. Systemic infusion of the designed complex would take it to tumor site where tripeptide at one end of ELP will bind to integrin protein present in the millieu of the cancer cells. Integrin bound macromolecular carrier would then facilitate entry into tumor cells via integrin receptors present on their membranes.