Journal
BIOCONJUGATE CHEMISTRY
Volume 21, Issue 3, Pages 489-495Publisher
AMER CHEMICAL SOC
DOI: 10.1021/bc9003958
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Funding
- National Cancer Institute
- National Institutes of Health [1 R01 CA119409]
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A targeted dendrimeric anticancer prodrug, a conjugate of generation 5 (G5) polyamidoamine (PAMAM) dendrimer, folic acid (FA), and methotrexate (MTX), has been successfully synthesized by using a novel one pot approach which is simple, reproducible, and feasible for large-scale synthesis. All dendrimer products have been characterized by H-1 NMR, MALDI-TOF, GPC, and HPLC. With this new method, the ratio of FA versus MTX attached to the dendrimer can be easily tuned to achieve the desired therapeutic effect. A new analytical approach for calculating the numbers of FA and MTX attached to the Dendrimer has been established. In Vitro studies performed oil FA receptor-expressing KB cells show that the new conjugate has a similar affinity and cytotoxic potency to G5-FA-MTX synthesized using the traditional multiple-step approach.
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