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Anticancer Drugs. 2010 Feb;21(2):186-92. doi: 10.1097/CAD.0b013e328334560f.

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

Author information

  • 1Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan Medical School, BSRB, Ann Arbor, MI 48109, USA. myca@umich.edu

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.

PMID:
20010426
[PubMed - indexed for MEDLINE]
PMCID:
PMC2818998
Free PMC Article

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