A specialized G-rich DNA structure, G-quadruplex, has been studied for its special physical characteristics and biological effects. Herein 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 could be physically conjugated with six molecules of porphyrin derivative, 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin (TMPyP4), to fabricate the apt-TMP complex. The TMPyP4 molecules in the complex were identified to bind tightly to the aptamer by intercalation and outside binding. Because the G-quadruplex structure is known to target the overexpressed nucleolin in cancer cells, in this study, the effect of the G-quadruplex structure as a carrier for the delivery of TMPyP4 into cancer cells by nucleolin-mediated internalization was investigated. The results showed that the apt-TMP complex exhibited a higher TMPyP4 accumulation in MCF7 breast cancer cells than in M10 normal epithelium cells. After treated with light for 180 s, the photodamage in MCF7 cells was larger than in M10 cells. These results indicated that the TMPyP4 delivery and uptake were mediated by the specific interaction of the apt-TMP complex with nucleolin on the cellular surface and that the use of the AS1411 aptamer as a drug carrier may be a potential tactic in cancer therapy.
A specialized G-quadruplex DNA aptamer with nucleolin targeting ability, AS1411, has been studied for cancer therapy. In this study, we report a novel delivery strategy for chemo-photodynamic combined treatment using AS1411 aptamer conjugated with tetra-(N-methyl-4-pyridyl)-porphine by intercalation and outside binding. Our results show that the apt-TMP complex exhibited higher TMPyP4 accumulation in nucleolin over-expressing MCF-7 breast cancer cells than in M10 normal epithelium cells. After irradiation for 180 sec, the photodamage was apparently observed in MCF-7 cells. These results indicate that AS1411 aptamer can play as a potential photosensitizer carrier for for cancer therapy.
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