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Targeting the efficacy of a dendrimer-based nanotherapeutic in heterogeneous xenograft tumors in vivo

Myc, Andrzej; Kukowska-Latallo, Jolanta; Cao, Peter; Swanson, Ben; Battista, Julianna; Dunham, Thomas; Baker, James R. Jr

Anti-Cancer Drugs:
doi: 10.1097/CAD.0b013e328334560f
Preclinical Reports
Abstract

Our earlier studies have shown the in vitro and in vivo targeting of a generation 5 (G5) dendrimer-based multifunctional conjugate that contained folic acid (FA) as the targeting agent and methotrexate (MTX) as the chemotherapeutic drug. To clinically apply the synthesized G5-FA-MTX nanotherapeutic, it is important that the anticancer conjugate elicits cytotoxicity specifically and consistently. Toward this objective, we evaluated the large-scale synthesis of a G5-FA-MTX conjugate (Lot # 123–34) for its cytotoxic potential and specificity in vitro and in vivo. The cytotoxicity and specificity were tested by using a coculture assay in which FA receptor-expressing and nonexpressing cells (KB and SK-BR-3 cells, respectively) were cultured together and preferential killing was examined. The in-vitro data were compared with the in-vivo data obtained from a heterogeneous xenograft tumor model. The animal model of the artificial heterogeneous xenograft tumor showed that the nanotherapeutic was preferentially cytotoxic to KB cells.

Author Information

Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan Medical School, BSRB, Ann Arbor, Michigan, USA

Correspondence to Andrzej Myc, PhD, MNIMBS, Rm 9346 MSRB III, University of Michigan, Ann Arbor, MI 48109, USA

Tel: +1 734 647 0052; fax: +1 734 936 2990; e-mail: myca@umich.edu

Andrzej Myc and Jolanta Kukowska-Latallo contributed equally to the study

Received 23 July 2009 Revised form accepted 19 October 2009

© 2010 Lippincott Williams & Wilkins, Inc.