Self-assembled DNA nanowires as quantitative dual-drug nanocarriers for antitumor chemophotodynamic combination therapy

Abstract

To combine cocktail chemotherapy and photodynamic therapy into one biocompatible and biodegradable nanocarrier, self-assembled DNA nanowires were fabricated and co-loaded with a photosensitizer chlorin e6 (Ce6) and a chemotherapeutic drug doxorubicin (DOX) for antitumor chemophotodynamic combination therapy. Two short DNA chains served as building blocks for the self-assembly of DNA nanowires in a supersandwich hybridization reaction that led to the successful formation of linear DNA nanowires of 500 bases, equal to a length of 167 nm. Ce6 and DOX were loaded onto the nanowires through covalent or noncovalent intercalation interactions, respectively. The DNA nanowires were taken up into cells, and the released Ce6 and DOX were ultimately distributed in different cellular compartments. The photosensitizer-loaded nanowires demonstrated increased generation of photodynamic reactive oxygen species (ROS) compared to that of free Ce6. In comparison with chemo- or photodynamic therapy alone, the combined treatment provided by DNA nanowires loaded with dual-drug significantly increased the incidence of HepG-2 cell death and produced a clear synergistic effect in the treatment of cancer cells. The DNA nanowire nanocarrier provided a flexible and quantitative drug-loading module that allowed for dose control of both drugs. More importantly, the DNA nanowires demonstrate a strong synergistic effect in antitumor chemophotodynamic combination therapy, likely because of increased photodynamic ROS generation and the distribution of Ce6 and DOX in different intracellular compartments. This work suggests that DNA nanowires may be useful as multifunctional and effective therapeutic nanocarriers for chemophotodynamic modalities in cancer therapy.