Multifunctional Self-Assembled DNA Nanospheres for Glioma Fluorescence/Magnetic Resonance Imaging and Therapy

DNA molecules can form predictable nanostructures through sequence-directed hybridization. In this study, DNA nanospheres were designed for fluorescence/magnetic resonance imaging and drug delivery in glioma-bearing mice. DNA nanospheres were constructed using Y-shaped DNA, linker DNA, and an DNA aptamer through the hybridization of their sticky ends. Linker DNA was assembled by an i-motif sequence with its complementary strand and could cause pH-responsive dissociation of double strands. The DNA aptamer with a sticky end could inhibit the extension of nanospheres to control their size as well as recognize glioma cells. Gd-DOTA, Cy5, and BHQ-3 were modified at specific bases to endow DNA nanospheres with dual imaging capabilities. Doxorubicin was loaded into DNA double strands, which were readily released in acidic environments. In vitro experiments revealed that the multifunctional nanospheres were pH-responsive and showed effective cell uptake and fluorescence and magnetic resonance imaging abilities. As drug carriers, DNA nanospheres increased the potency of doxorubicin against glioma cells. This approach achieved dual imaging and therapeutic effects in xenograft glioma mice by integrating multiple functions and may provide guidance for the surgical resection of glioma and assist with postoperative chemotherapy.