Targeted Dendrimeric Anticancer Prodrug: A Methotrexate-Folic Acid-Poly(amidoamine) Conjugate and a Novel, Rapid, One Pot Synthetic Approach

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.