Organelle-Specific Triggered Release of Immunostimulatory Oligonucleotides from Intrinsically Coordinated DNA–Metal–Organic Frameworks with Soluble Exoskeleton

DNA has proven of high utility to modulate the surface functionality of metal–organic frameworks (MOFs) for various biomedical applications. Nevertheless, current methods for preparing DNA–MOF nanoparticles rely on either inefficient covalent conjugation or specific modification of oligonucleotides. In this work, we report that unmodified oligonucleotides can be loaded on MOFs with high density (∼2500 strands/particle) via intrinsic, multivalent coordination between DNA backbone phosphate and unsaturated zirconium sites on MOFs. More significantly, surface-bound DNA can be efficiently released in either bulk solution or specific organelles in live cells when free phosphate ions are present. As a proof-of-concept for using this novel type of DNA–MOFs in immunotherapy, we prepared a construct of immunostimulatory DNA–MOFs (isMOFs) by intrinsically coordinating cytosine–phosphate–guanosine (CpG) oligonucleotides on biocompatible zirconium MOF nanoparticles, which was further armed by a protection shell of ca...