A Novel AS1411 Aptamer-Based Three-Way Junction Pocket DNA Nanostructure Loaded with Doxorubicin for Targeting Cancer Cells in Vitro and in Vivo.
Seyed Mohammad TaghdisiNoor Mohammad DaneshMohammad RamezaniRezvan Yazdian-RobatiKhalil AbnousPublished in: Molecular pharmaceutics (2018)
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.
Keyphrases
- circulating tumor
- drug delivery
- cancer therapy
- cell free
- single molecule
- induced apoptosis
- nucleic acid
- gold nanoparticles
- prostate cancer
- wound healing
- circulating tumor cells
- single cell
- signaling pathway
- oxidative stress
- cell proliferation
- mesenchymal stem cells
- bone marrow
- anti inflammatory
- magnetic nanoparticles
- pi k akt