Aptamer-based tumor-targeted drug delivery for photodynamic therapy
Journal
ACS Nano
Journal Volume
4
Journal Issue
3
Pages
1433-1442
Date Issued
2010
Author(s)
Abstract
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. ? 2010 American Chemical Society.
Subjects
5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin; Aptamer; Nucleolin; Photodynamic therapy
SDGs
Other Subjects
5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin; Aptamers; Biological effects; Cancer cells; Cancer therapy; DNA structure; Drug carrier; Epithelium cells; G-quadruplex structure; G-quadruplexes; MCF-7 breast cancer cells; MCF-7 cells; Novel strategies; Nucleolin; Outside binding; Photo-damage; Physical characteristics; Porphyrin derivatives; Specific interaction; Targeted drug delivery; Tetrakis; Cells; Complexation; Drug delivery; Drug interactions; Optical materials; Plasmons; Porphyrins; Special effects; Thermomechanical pulping process; Photodynamic therapy; aptamer; drug carrier; guanine quadruplex; ligand; nucleolin; phosphoprotein; porphyrin; RNA binding protein; tetra(4 N methylpyridyl)porphine; tetra(4-N-methylpyridyl)porphine; antibody specificity; article; cell nucleus; chemistry; circular dichroism; flow cytometry; gene expression regulation; genetics; human; metabolism; methodology; neoplasm; nucleotide sequence; pathology; photochemotherapy; transmission electron microscopy; transport at the cellular level; tumor cell line; ultraviolet spectrophotometry; Aptamers, Nucleotide; Base Sequence; Biological Transport; Cell Line, Tumor; Cell Nucleus; Circular Dichroism; Drug Carriers; Flow Cytometry; G-Quadruplexes; Gene Expression Regulation, Neoplastic; Humans; Ligands; Microscopy, Electron, Transmission; Neoplasms; Organ Specificity; Phosphoproteins; Photochemotherapy; Porphyrins; RNA-Binding Proteins; Spectrophotometry, Ultraviolet
Type
journal article