DNA Nanoflower Enables Controlled Co‐Delivery of Antisense Oligodeoxynucleotide and Doxorubicin for Anti‐Breast Cancer Treatment

ABSTRACT Doxorubicin (DOX), an anthracycline antibiotic, is widely used to treat a range of solid tumours and haematological malignancies. However, its clinical application in breast cancer is hindered by toxic side effects and the development of multidrug resistance (MDR). Enhancing the selective targeting of DOX and overcoming MDR are critical to improving treatment efficacy. Here, we present a DNA nanoflower (DNF)‐based delivery system, designed via rolling circle amplification and multi‐primer amplification (MCA), which co‐delivers antisense oligonucleotides (ASOs) and DOX to human breast cancer cells (MCF‐7). This system, named DNF‐ASO@DOX, effectively promotes gene silencing, enhances drug accumulation and significantly inhibits cell proliferation. Furthermore, in vivo studies using mouse models of breast cancer demonstrated potent therapeutic effects, highlighting DNF‐ASO@DOX as a promising strategy for enhanced anti‐tumour therapy.