Metabolic limitations of the use of nucleoside analogs in cancer therapy may be overcome by application of nanoparticles as drug carriers: A review

Abstract

Purine and pyrimidine nucleoside analogs (NAs) are antimetabolites commonly used in cancer therapy. Administered as prodrugs, NAs permeate the mambrane using specialized transporters. Following phosphorylation, they interfere with multiple cellular pocessess inducing cytotoxicity. Toxic effects of NAs are dependent on metabolic conversion from a prodrug into the active form. For instance, an exceptionally high activity of deoxycytidine kinase (dCK) in lymphocytes is correlated with a good therapeutic effect of fludarabine in leukemic cells. On the other hand, several studies have shown that nucleoside-transporter (NT)-deficientcells are highly resistant to NAs. Attempts to overcome the metabolic limitations of chemotherapeutics would result in the use of lower drug doses for effective therapy, reduce side effects, and ensure the independence of drug resistance mechanisms. To meet this need, several nanoparticles have been designed to deliver efficently NAs directly to cancer cells. Such vehicles include liposomes, albumins, and dendritic and linear polymers. Therapeutic agents encapsulated or conjugated to nanoparticles have improved pharmacokinetics, solubility, and stability. These factors improve the efficacy of commonly used drugs. Moreover, modification of nanoparticles with targeting molecules such as sugar moieties or folic acid ensures more specific delivery without affecting healthy tissues. Drug Dev Res 71:383-394, 2010.

Aberrant Apoptotic Response of Colorectal Cancer Cells to Novel Nucleoside Analogues

“…Nucleoside analogues are an important class of chemotherapeutic agents used in the treatment of cancer and viral infections [ 23 , 24 , 25 ]. This study identified novel nucleoside analogues that proved to be cytotoxic and able to induce an unusual apoptotic response with the concurrent formation of cytoplasmic vacuoles in two colorectal adenocarcinoma cell lines.…”

Characteristics of complexes between poly(propylene imine) dendrimers and nucleotides

“…They penetrate into the cell through nucleoside transporters (NTs). 12,13 Then, in a cell, NAs are phosphorylated by deoxycitidine kinase (dCK), monophosphate kinases (NMPKs) and diphosphate kinases (NDPKs) to 5 0 -mono-, diand triphosphates. 1,2,4 All NAs have a similar mechanism of activity (Fig.…”

Multifunctional Drug Delivery Systems Using Inorganic Nanomaterials: A Review

“…This results in serious side effects on other critical normal tissues such as bone marrow, kidney, liver and cardiac tissues. 12 Therefore, searching for novel approach for safe and accurate diagnosis of earlystage cancer and targeted therapies has been exciting yet challenging area of research.…”