Journal
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
Volume 63, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.jddst.2021.102521
Keywords
Linear DNA nanostructure; Combination therapy; Chemotherapy drug; Therapeutic oligonucleotides
Categories
Funding
- Mashhad University of Medical Sciences
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A novel linear DNA nanostructure-based delivery system was designed to efficiently co-deliver chemotherapy drug Epi and therapeutic oligonucleotide antimiR-10b into breast cancer cells, showing high stability, strong targeting ability, and significant inhibition of tumor growth.
Herein, a novel linear DNA nanostructure (LDN)-based delivery system was designed and prepared to efficiently co-deliver both epirubicin (Epi), as a chemotherapy drug, and antimiR-10b, as a therapeutic oligonucleotide, into breast cancer cells (MCF-7 and 4T1 cells). Firstly, the LDN, comprised of AS1411 aptamer (targeting agent), FOXM1 Apt (therapeutic aptamer), and complementary strand (linker), was prepared to carry both Epi and antimiR-10b. This targeted system is highly stable in serum and easy to be constructed. The Epi-loaded LDN structure showed a remarkable internalization for target cells (MCF-7 and 4T1 cells, nucleolin positive) in comparison with CHO cells (nucleolin negative, non-target). Furthermore, based on the MTT assay, the Epiloaded LDN significantly decreased the cell viability of MCF-7 and 4T1 cells, while the non-targeted cells indicated less cytotoxicity for this structure, showing the targeting ability of Epi-loaded LDN. Moreover, the ability of tumor growth inhibition of the Epi-loaded LDN structure was significantly much more than free Epi and LDN in tumor-bearing mice, suggesting the significance of combination therapy for tumor treatment.
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