A Platform of G-quadruplex DNA Aptamer for Targeted Drug-Delivery
Date Issued
2009
Date
2009
Author(s)
Shieh, Yen-An
Abstract
A specialized G-rich DNA structure, G-quadruplex, has been studied for its special physical characters and biological effect. Here we report a novel strategy of using G-quadruplex as a drug carrier to target cancer cells for photodynamic therapy (PDT). A G-quadruplex forming AS1411 aptamer was physical conjugated with six of porphyrin derivative, tetra-(N-methyl-4-pyridyl)-porphine (TMPyP4), to fabricate the apt-TMP complex. The complex was identified that TMPyP4 molecules was bound tightly to aptamer by intercalation and outside binding by the UV-Vis spectrophotometry, fluorescence spectrophotometer and circular dichroism (CD) spectroscopy. Because the G-quadruplex structure of AS1411 is known to target to nucleolin over-expressed in cancer cells, in this study, the effect of G-quadruplex structure as a carrier for delivery of TMPyP4 into cancer cells by nucleolin-mediated internalization was investigated. Results from flow cytometry and fluorescent microscopy showed that the apt-TMP complex exhibited higher TMPyP4 accumulation in MCF7 breast cancer cells than in M10 normal epithelium cells. The effective inhibition of TMPyP4 uptake from MCF7 cells was further observed by adding an excess of free aptamer or monoclonal anti-nucleolin antibody. After treated with light for 180 sec, the photodamage in MCF7 cells was larger than in M10 cells. These results indicate that TMPyP4 delivery and uptake were mediated by the specific interaction of apt-TMP complex with nucleolin on the cellular surface and the use of G-quadruplex forming AS1411 aptamer as a drug carrier may be a potential tactic for cancer therapy.
Subjects
aptamer
drug delivery
nucleolin
photodynamic therapy
SDGs
Type
thesis
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