Aptamer-based tumor-targeted drug delivery for photodynamic therapy.
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.
Shieh
Yen-An
YA
Institute of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei 10051, Taiwan.
Yang
Shu-Jyuan
SJ
Wei
Ming-Feng
MF
Shieh
Ming-Jium
MJ
D052157:Aptamers, Nucleotide / Q000737:chemistry* / Q000235:genetics; D001483:Base Sequence; D001692:Biological Transport; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D002942:Circular Dichroism; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D005434:Flow Cytometry; D054856:G-Quadruplexes; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008024:Ligands; D046529:Microscopy, Electron, Transmission; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009928:Organ Specificity; D010750:Phosphoproteins / Q000378:metabolism; D010778:Photochemotherapy / Q000379:methods*; D011166:Porphyrins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D016601:RNA-Binding Proteins / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet; D000097796:Nucleolin
D052157:Aptamers, Nucleotide; D004337:Drug Carriers; D008024:Ligands; D010750:Phosphoproteins; D011166:Porphyrins; D016601:RNA-Binding Proteins; D000097796:Nucleolin; C021096:tetra(4-N-methylpyridyl)porphine