Abstract
Aptamers offer a great opportunity to develop innovative drug delivery systems that can deliver cargos specifically into targeted cells. In this study, a chimera consisting of two aptamers was developed to deliver doxorubicin into cancer cells and release the drug in cytoplasm in response to adenosine-5′-triphosphate (ATP) binding. The chimera was composed of the AS1411 anti-nucleolin aptamer for cancer cell targeting and the ATP aptamer for loading and triggering the release of doxorubicin in cells. The chimera was first produced by hybridizing the ATP aptamer with its complementary DNA sequence, which is linked with the AS1411 aptamer via a poly-thymine linker. Doxorubicin was then loaded inside the hybridized DNA region of the chimera. Our results show that the AS1411–ATP aptamer chimera was able to release loaded doxorubicin in cells in response to ATP. In addition, selective uptake of the chimera into cancer cells was demonstrated using flow cytometry. Furthermore, confocal laser scanning microscopy showed the successful delivery of the doxorubicin loaded in chimeras to the nuclei of targeted cells. Moreover, the doxorubicin-loaded chimeras effectively inhibited the growth of cancer cell lines and reduced the cytotoxic effect on the normal cells. Overall, the results of this study show that the AS1411–ATP aptamer chimera could be used as an innovative approach for the selective delivery of doxorubicin to cancer cells, which may improve the therapeutic potency and decrease the off-target cytotoxicity of doxorubicin.
Highlights
Introduction published maps and institutional affilThe coining of the “magic bullet” concept inspired generations of researchers to develop treatments with reduced toxicity and enhanced therapeutic efficacy
DNA strand, which has been linked to the AS1411 aptamer, for specific targeting of the domain for doxorubicin by annealing the Adenosine triphosphate (ATP) DNA aptamer and its complementary DNA
The control chimera CRO–ATPapt was generated, where the AS1411 strand, which has been linked to the AS1411 aptamer, for specific targeting of the chimera
Summary
DNA strand, which has been linked to the AS1411 aptamer, for specific targeting of the domain for doxorubicin by annealing the ATP DNA aptamer and its complementary DNA chimera. This was detected between annealing step between the ATP DNA aptamer and its complementary DNA sequence, the Cy5 dye conjugated to ATP aptamer and the Iowa black RQ quencher This was detected between the Cy5 dye quencher for Cy5) conjugated to the complementary DNA sequence. Quenching-based triggering dissociation of ATP aptamer from its complementary DNA strand.
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