Efficient synthesis of artificial pharmaceutical solid-phase modules for constructing aptamer-drug conjugates

As a promising targeted drug delivery system, aptamer-drug conjugates (ApDCs) can specifically bind with cognate molecular targets for improving therapeutic efficacy and reducing drug toxicity. However, current ApDC strategies suffer from problems caused by the complicated synthesis, relatively high cost, low controllability of drug binding sites and loading ratio. To solve these difficulties, we have designed and synthesized an artificial pharmaceutical solid-phase module of Combretastatin A-4 (CA-4), in which an inactive ingredient was selected as bonding moiety to incorporate with solid phase functionalities. Through solid-phase synthesis technology, this module was automatically and efficiently conjugated with an aptamer at predesigned positions. Biological studies revealed that these ApDCs can not only maintain excellent specific recognition ability, but also possess definite cytotoxicity against tumor cells.