A Novel AS1411 Aptamer-Based Three-Way Junction Pocket DNA Nanostructure Loaded with Doxorubicin for Targeting Cancer Cells in Vitro and in Vivo.

Abstract

Active targeting of nanostructures containing chemotherapeutic agents can improve cancer treatment. Here, a three-way junction pocket DNA nanostructure was developed for efficient doxorubicin (Dox) delivery into cancer cells. The three-way junction pocket DNA nanostructure is composed of three strands of AS1411 aptamer as both a therapeutic aptamer and nucleolin target, the potential biomarker of prostate (PC-3 cells) and breast (4T1 cells) cancers. The properties of the Dox-loaded three-way junction pocket DNA nanostructure were characterized and verified to have several advantages, including high serum stability and a pH-responsive property. Cellular uptake studies showed that the Dox-loaded DNA nanostructure was preferably internalized into target cancer cells (PC-3 and 4T1 cells). MTT cell viability assay demonstrated that the Dox-loaded DNA nanostructure had significantly higher cytotoxicity for PC-3 and 4T1 cells compared to that of nontarget cells (CHO cells, Chinese hamster ovary cell). The in vivo antitumor effect showed that the Dox-loaded DNA nanostructure was more effective in prohibition of the tumor growth compared to free Dox. These findings showed that the Dox-loaded three-way junction pocket DNA nanostructure could significantly reduce the cytotoxic effects of Dox against nontarget cells.

• Authors: Seyed Mohammad Taghdisi, Noor Mohammad Danesh, Mohammad Ramezani, Rezvan Yazdian-Robati, Khalil Abnous
• Journal: Molecular pharmaceutics (Mol Pharm) Vol. 15 Issue 5 Pg. 1972-1978 (05 07 2018) ISSN: 1543-8392 [Electronic] United States
• PMID: 29669200 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• AGRO 100
• Aptamers, Nucleotide
• DNA Adducts
• Drug Carriers
• Oligodeoxyribonucleotides
• Phosphoproteins
• RNA-Binding Proteins
• doxorubicin-DNA
• Doxorubicin
• DNA

Topics

• Animals
• Aptamers, Nucleotide (chemistry)
• Breast (chemistry)
• Breast Neoplasms (drug therapy)
• CHO Cells
• Cell Line, Tumor
• Cell Survival (drug effects)
• Cricetulus
• DNA (chemistry)
• DNA Adducts (chemistry)
• Doxorubicin (chemistry, pharmacology)
• Drug Carriers (chemistry)
• Drug Delivery Systems (methods)
• Female
• Humans
• Male
• Mice
• Mice, Inbred BALB C
• Nanoparticles (chemistry)
• Nanostructures (chemistry)
• Oligodeoxyribonucleotides (chemistry)
• Phosphoproteins (chemistry)
• Prostatic Neoplasms (drug therapy)
• RNA-Binding Proteins (chemistry)
• Nucleolin