Engineering hierarchical metal-organic@metal-DNA heterostructures for combinational tumor treatment
Xueyan Feng, Bei Liu, Zehao Zhou, Wei Li, Jian Zhao, Lele Li, Yuliang Zhao
Abstract
Development of simple methods for controlled integration of DNA molecules with metal-organic frameworks (MOFs) is important for various biomedical applications, yet remains a challenge. Herein, a simple and general approach to load DNA on the surface of MOFs is developed via one-pot self-assembly of DNA and Feǁ ions on nanoscale MOFs, resulting in hierarchical core-shell nanostructures of metal-organic@metal-DNA coordination polymers. The strategy enables assembly of DNA molecules on MOFs with ultra-high contents and precise controllability. By incorporation of a chemotherapeutic drug into the Fe-DNA shell, the systems allow to integrate chemotherapy and gene therapy with photodynamic therapy for combinational tumor treatment. Moreover, the hybrid nanostructures enable light-triggered production of cytotoxic singlet oxygen, which further boosts the endosomal escape of the system for an enhanced gene silencing efficacy and thus improved therapeutic outcome. This work highlights a robust approach for the construction of coordination-based drug delivery systems to combat tumor.