Multicomponent targeted proapoptotic anticancer drug delivery system

Cancer is one of the leading causes of death in United States. The current approaches for the treatment of solid tumor available are the surgery for the removal of primary tumor followed by chemotherapy and /or radiation. The efficacy of chemotherapy is limited by the following factors; (1) adverse side-effects on healthy organs, (2) development of cellular resistance and (3) low solubility of many anticancer drugs. The primary objective of this dissertation is to overcome all the above stated limitations. The methods employed in this dissertation includes designing, synthesizing and evaluating a novel drug delivery system comprising of 1) multiple copies of an anticancer drug, Camptothecin (CPT) ; 2) a polymeric carrier, Polyethylene glycol (PEG); 3) multiple copies of a targeting moiety to cancer cells, Luteinizing hormone releasing hormone (LHRH) peptide; 4) multiple copies of a suppressor of antiapoptotic cellular defense, BH3 peptide both in vitro and in vivo on A2780 human ovarian carcinoma cells and malignant ascites and animal models respectively. Conjugates of CPT, LHRH and CPT, LHRH, BH3 were evaluated for cytotoxicity, cancer specificity and antitumor activity. The multicomponent anticancer delivery system will significantly enhance the efficacy of an anticancer drug in the treatment of all the stages of cancer when compared with free drug, non-targeted delivery systems or the system consisting of one copy of each active component.Ph.D.Includes bibliographical referencesIncludes vitaby Pooja Chandn