Smart Magnetic Nanoaptamer: Construction, Subcellular Distribution, and Silencing HIF for Cancer Gene Therapy.

Attenuating the expression of HIF-1α (hypoxic inducible factor) by siRNA has an effect on the proliferation of hypoxia cancers. Mitochondria targeting siRNA may silence the level of HIF-1α for cancer gene therapy. A GAG-rich DNA was conjugated to GC-rich DNA for the synthesis of functional magnetic nanoaptamer (DNA-Fe3O4) to keep the innate character of the targeting aptamer. The DNA-Fe3O4 can load the hydrophobic dye (BODIPY-OCH3) by the GC-rich sequences, resulting in fluorescent nanoaptamer (BFe@DNA). Self-assembly of BFe@DNA with target aptamer resulted in the formation of BFe@DNAH. Subcellular fluorescence imaging results confirm that BFe@DNAH can accumulate in MCF-7 cells and selectively target mitochondrion. In particular, BFe@DNAH can transport siRNA to breast cancer cells or tissues for the attenuation of HIF-1α and ATP and the inhibition on growth of cancer cells in vivo. Therefore, BFe@DNAH is a smart nanoaptamer platform for the development of subcellular imaging agents and gene therapy.