Multifunctional DNA Polycatenane Nanocarriers for Synergistic Targeted Therapy of Multidrug‐Resistant Human Leukemia

Abstract

AbstractChemotherapy, as one of the principal modalities for cancer therapy, is limited by its inefficient delivery, serious side effects as well as multidrug resistance (MDR). Herein, multifunctional aptamer‐tethered deoxyribonucleic acids (DNA) polycatenanes (AptDPCs) is reported to combat MDR human leukemia. By rational design, the DNA polycatenanes (DPCs) are first constructed by a one‐step self‐assembly approach, during which DPCs are incorporated with fluorophores for bioimaging, abundant doxorubicin (DOX) intercalation sites for drug delivery, and antisense oligonucleotides (AS ODNs) for inhibiting the expression of P‐glycoprotein (P‐gp) and further reversing MDR. In addition, to endow the DPCs with specific recognition toward the target cancer cells and high purity, aptamers are tethered to the DPCs via the magnetic separation method based on the toehold‐mediated strand displacement (TMSD) reaction, which not only improves the purity and reproducibility of the AptDPCs, but also realizes the recycle of magnetic carriers. The results confirm that the AptDPCs can deliver drugs and AS ODNs into the target cancer cells and synergistically inhibit the MDR tumor growth without apparent systematic toxicity. The proposed AptDPC‐based drug delivery system can effectively reduce side effects and reverse MDR, which provides a promising platform for codelivery of therapeutic genes and chemodrugs in targeted cancer therapy.