POLY 323 |
| We have designed, synthesized and evaluated a novel targeted polymeric prodrug which can contain several copies of active ingredients. The prodrug consists of: (1) poly(ethylene glycol) (PEG) polymer as a carrier; (2) synthetic analog of luteinizing hormone releasing hormone (LHRH) peptide as a tumor targeting moiety; (3) camptothecin (CPT) as an anticancer drug and (4) BCL2 homology 3 domain (BH3) peptide as a suppressor of cellular antiapoptotic defense. We used citric acid as a multifunctional spacer to conjugate several copies of active ingredients to the PEG polymer. Experimental data obtained support the main hypothesis that simultaneous suppression of cellular antiapoptotic defense combined with tumor targeting substantially enhances specific antitumor efficacy of an anticancer drug. The complex targeted proapoptotic anticancer drug delivery system, which contains several copies of CPT and LHRH, can be used in chemotherapy directed against tumors that overexpress LHRH receptors. This multifunctional approach can be used for other drugs, targeting moieties, imaging agents and active ingredients. |
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7th International Biorelated Polymers Symposium
8:30 AM-12:10 PM, Tuesday, 12 September 2006 San Francisco Marriott -- Salon 14/15, Oral
Division of Polymer Chemistry |