# Selective Delivery of Anticancer Natural G‑Quadruplex Ligands by the AT11 Aptamer for Gastric Cancer Treatment

## TL;DR

This study explores how natural compounds can be selectively delivered to cancer cells using a G-quadruplex aptamer to improve anticancer treatment.

## Contribution

The paper introduces a novel approach using the AT11 aptamer to selectively deliver natural G-quadruplex ligands to cancer cells.

## Key findings

- Natural compounds like bulbocapnine and chelidonine preferentially interact with the 3′-end G-quartet of the AT11 aptamer.
- The AT11/natural compound complexes significantly reduced gastric cancer cell viability with minimal impact on noncancerous cells.
- Synergistic effects were observed in cancer cell inhibition when using the AT11/aptamer complexes.

## Abstract

Searching for G-quadruplex-selective ligands as anticancer
agents,
we recently identified the natural compounds bulbocapnine, chelidonine,
dicentrine, ibogaine, and rotenone as novel interactors of G-quadruplexes.
Herein, to investigate their ability to interact with a specific carrier
for selective delivery to cancer cells, the dimeric G-quadruplex-forming
aptamer AT11 was used as a model. NMR spectroscopy, molecular modeling,
circular dichroism, and fluorescence spectroscopy allowed the preferential
interaction to be proven with the 3′-end G-quartet for bulbocapnine,
chelidonine, dicentrine, and ibogaine, whereas with the 5′-end
G-quartet region for rotenone. The anticancer activity of the AT11/natural
compounds complexes was evaluated on gastric cancer cells using the
free aptamer and free natural compounds as controls. Notably, all
complexes caused a significant decrease in cancer cell viability,
also producing synergistic effects. Remarkably, no relevant effects
were detected on noncancerous cells, denoting the importance of delivering
the natural compounds by AT11 G-quadruplex to obtain selective antiproliferative
effects on cancer vs. normal cells.