Metal "X" Frameworks (MXFs) constructed from metal ions and biomacromolecules ("X components") via coordination interactions show crystalline structures and diverse functionalities. Here, a series of MXFs composed of various metal ions (e.g., Zn2+, Hf4+, Ca2+) and DNA oligodeoxynucleotides were reported. With MXF consisting of Hf4+ and CpG oligodeoxynucleotides as the example, we show that such Hf-CpG MXF can achieve high-Z elements-enhanced photon radiotherapy and further trigger robust tumor-specific immune responses, thus showing efficient tumor suppression ability. In vivo experiments showed that external beam radiotherapy applied on tumors locally injected with Hf-CpG MXF result in the thorough elimination of primary tumors, complete inhibition of tumor metastasis, and protection against tumor rechallenge by triggering robust antitumor immune responses. Our findings provide a blueprint for fabricating a variety of rationally designed MXFs with desired functions and present the strategy of stimulating whole-body systemic immune responses by only local treatment of radiotherapy.
Keywords: Cancer immunotherapy; DNA nanotechnology; Metal “X” Frameworks (MXFs); Metal−organic frameworks (MOFs); Radiotherapy.