Aptamers as Targeting Delivery Devices or Anti-cancer Drugs for Fighting Tumors

Bruna      Scaggiante; Barbara      Dapas; Rossella      Farra; Mario      Grassi; Gabriele      Pozzato; Carlo      Giansante; Nicola      Fiotti; Elisa      Tamai; Federica      Tonon; Gabriele      Grassi

Abstract

Aptamer researches applied to the treatment of human cancers have increased since their discovery in 1990. This is due to different factors including: 1) the technical possibility to select, by SELEX-based procedures, specific aptamers targeting virtually any given molecule, 2) the aptamer favorable bio-activity in vivo, 3) the low production costs and 4) the ease synthesis and storage for the marketing. In the field of cancer treatments, aptamers have been studied as tumor-specific agents driving drugs into cancer cells; additionally they have been used as anti-neoplastic agents, able to inhibit tumor cell growth and dissemination when administered alone or in combination with conventional anti-neoplastic drugs. Aptamers are gaining an increased interest for pharmaceutical companies and some of them are under clinical evaluation trials.

In this review we update the findings about the use of aptamers as “escort” molecules able to drive drugs into the cells and as antineoplastic drugs. Current anti-neoplastic treatments suffer from the intrinsic toxicity related to the un-specific targeting of both normal and tumorigenic proliferating cells. The aptamers could be useful to improve: 1) the selective targeting of molecules essential for the viability and expansion of tumor cells and/or the selective driving of chemotherapies into tumor cells, thus resulting in higher effectiveness and lower systemic side-effects compared to conventional anti-neoplastic drugs alone and 2) to improve the therapeutic index of currently used chemotherapies. Even if some problems related to the in vivo stability and pharmacokinetic/dynamics of aptamers remain to be improved, their potential use in the treatment of different human cancers is getting closer and closer to a practical therapeutic use.

Keywords: Aptamer, chemical analogues, SELEX, drug delivery, tumors, PSMA, nucleolin, eEF1A.