PRECLINICAL REPORTSIn-vivo antitumour effect of daunorubicin–GnRH-III derivative conjugates on colon carcinoma-bearing miceManea, Marilenaa,b; Tóvári, Józsefc; Tejeda, Miguelc; Schulcz, Ákosc; Kapuvári, Bencec; Vincze, Borbálac; Mező, Gábord Author Information aLaboratory of Analytical Chemistry and Biopolymer Structure Analysis, Department of Chemistry bZukunftskolleg, University of Konstanz, Konstanz, Germany cNational Institute of Oncology dResearch Group of Peptide Chemistry, Hungarian Academy of Sciences, Eötvös L. University, Budapest, Hungary Correspondence to Dr Gábor Mező, PhD, DSc, Research Group of Peptide Chemistry, Hungarian Academy of Sciences, Eötvös L. University, 1117 Budapest, Pázmány P. stny. 1/A, Hungary Tel: +36 1 372 2500 x 1433; fax: +36 1 372 2620; e-mail: [email protected] Received April 5, 2011 Accepted August 8, 2011 Anti-Cancer Drugs: January 2012 - Volume 23 - Issue 1 - p 90-97 doi: 10.1097/CAD.0b013e32834bb6b4 Buy Metrics Abstract Targeted cancer chemotherapy is a novel approach developed for the specific delivery of anticancer drugs. Tumour targeting can be achieved by combining a chemotherapeutic agent with a targeting moiety that recognizes tumour-specific or highly expressed receptors on cancer cells. We used the gonadotropin-releasing hormone-III (GnRH-III) as a targeting moiety to which the chemotherapeutic agent daunorubicin (Dau) was attached through an oxime bond either directly or by inserting a GFLG tetrapeptide spacer. The in-vivo toxicity of Dau–GnRH-III derivative conjugates was evaluated on healthy BDF-1 female mice, and their tumour growth inhibitory effect was determined on C26 murine and HT-29 human colon carcinoma-bearing mice. Both oxime bond-containing conjugates were well tolerated and exerted significant antitumour activity on C26 colon carcinoma-bearing mice at a dose of 30 mg Dau content in conjugate/kg body weight. Furthermore, the conjugates inhibited the tumour growth more than the free drug at a dose that was still not toxic. Similar tumour growth inhibitory effects were obtained on HT-29 human colon carcinoma-bearing mice using three treatments with 15 mg Dau content in conjugate/kg. The tumour growth inhibitions according to the tumour volume and the tumour weight were 44/41% and 58/50%, respectively. Considering the results, both of the investigated Dau–GnRH-III derivative conjugates were well tolerated and had significant antitumour effect on colon carcinoma-bearing mice. © 2012 Lippincott Williams & Wilkins, Inc.