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Current Medicinal Chemistry

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ISSN (Online): 1875-533X

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Review Article

Oligonucleotides Carrying Nucleoside Antimetabolites as Potential Prodrugs

Author(s): Carme Fàbrega, Anna Clua, Ramon Eritja* and Anna Aviñó

Volume 30, Issue 11, 2023

Published on: 24 January, 2022

Page: [1304 - 1319] Pages: 16

DOI: 10.2174/0929867328666211129124039

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Abstract

Background: Nucleoside and nucleobase antimetabolites are an important class of chemotherapeutic agents for the treatment of cancer as well as other diseases.

Introduction: In order to avoid undesirable side effects, several prodrug strategies have been developed. In the present review, we describe a relatively unknown strategy that consists of using oligonucleotides modified with nucleoside antimetabolites as prodrugs.

Methods: The active nucleotides are generated by enzymatic degradation once incorporated into cells. This strategy has attracted large interest and is widely utilized at present due to the continuous developments made in therapeutic oligonucleotides and the recent advances in nanomaterials and nanomedicine.

Results: A large research effort was made mainly in the improvement of the antiproliferative properties of nucleoside homopolymers, but recently, chemically modified aptamers, antisense oligonucleotides and/or siRNA carrying antiproliferative nucleotides have demonstrated a great potential due to the synergetic effect of both therapeutic entities. In addition, DNA nanostructures with interesting properties have been built to combine antimetabolites and enhancers of cellular uptake in the same scaffold. Finally, protein nanoparticles functionalized with receptor-binders and antiproliferative oligomers represent a new avenue for a more effective treatment in cancer therapy.

Conclusion: It is expected that oligonucleotides carrying nucleoside antimetabolites will be considered as potential drugs in the near future for biomedical applications.

Keywords: Antimetabolites, nucleosides, nanomedicine, antiproliferative oligomers, homopolymers, floxuridine, gemcitabine, cytarabine.

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