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

摘要

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 ¹H 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 on 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.