Journal
CURRENT MEDICINAL CHEMISTRY
Volume 30, Issue 11, Pages 1304-1319Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/0929867328666211129124039
Keywords
Antimetabolites; nucleosides; nanomedicine; antiproliferative oligomers; homopolymers; floxuridine; gemcitabine; cytarabine
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Nucleoside and nucleobase antimetabolites are important chemotherapeutic agents for cancer treatment and other diseases. Prodrug strategies have been developed to avoid side effects. This review describes the use of nucleoside antimetabolite-modified oligonucleotides as prodrugs, which are enzymatically degraded to generate active nucleotides inside cells. It discusses the potential of these modified oligonucleotides in biomedical applications, including the improvement of antiproliferative properties and the development of DNA nanostructures and protein nanoparticles for enhanced cancer therapy.
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.
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