Anti-Cancer Drugs

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Anti-Cancer Drugs:
doi: 10.1097/CAD.0b013e3282f28842
Preclinical Reports

Preclinical antitumor efficacy evaluation of dendrimer-based methotrexate conjugates

Myc, Andrzej; Douce, Thomas B.; Ahuja, Niharika; Kotlyar, Alina; Kukowska-Latallo, Jolanta; Thomas, Thommey P.; Baker, James R. Jr

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Abstract

Our previous studies have demonstrated the in-vitro and in-vivo targeting of a generation-5 (G5) dendrimer-based multifunctional conjugate, which used folic acid (FA) as the targeting agent and methotrexate (MTX) as the chemotherapeutic drug. For the synthesized G5-FA-MTX nanodevice conjugate to be clinically applicable as a cancer therapeutic drug, it is important that the compound elicits cytotoxicity specifically and consistently. The aim of this work was to evaluate four independently synthesized batches of G5-FA-MTX conjugates for their cytotoxic potential and specificity. For determination of specificity, we have used a unique ‘coculture’ assay in which FA receptor-positive and FA receptor-negative cells were cultured together and have examined the preferential killing of the former. The results of our study show the batch-to-batch consistency and specificity of the G5-FA-MTX nanodevice in the preferential killing of FA receptor-positive cells. The coculture assay shows the consistency of the four different G5-FA-MTX conjugate lots in the specific killing of targeted cells. Further in-vivo studies are, however, necessary to prove the clinical potential of this targeted therapeutic nanodevice.

© 2008 Lippincott Williams & Wilkins, Inc.

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