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 calcium phosphate (CaP) exoskeleton. We demonstrated that isMOFs exhibited high cellular uptake, organelle specificity, and spatiotemporal control of Toll-like receptors (TLR)-triggered immune responses. When isMOF reached endolysosomes via microtubule-mediated trafficking, the CaP exoskeleton dissolved in the acidic environment and in situ generated free phosphate ions. As a result, CpG was released from isMOFs and stimulated potent immunostimulation in living macrophage cells. Compared with naked CpG–MOF, isMOFs exhibited 83-fold up-regulation in stimulated secretion of cytokines. We thus expect this isMOF design with soluble CaP exoskeleton and an embedded sequential “protect–release” program provides a highly generic approach for intracellular delivery of therapeutic nucleic acids.

Organic micropollutants are posing great challenges to global water resources, especially for non-biodegradable synthetic chemicals. In this study, a carboxyl-derived pillar[5]arene (P5) and p-phenylenediamine (PPD) were crosslinked to produce a 3D network polymer, P5-P, for the adsorption and removal of organic micropollutants from water. This 3D network polymer sequesters a variety of organic micropollutants in water with rapid adsorption rates and large uptake amounts, much greater than those of conventional activated carbon. Especially, this polymer demonstrates superior adsorption performance for fluorescein sodium and methyl orange and it can be fully regenerated multiple times by a mild washing procedure. The structure of this 3D network polymer and its adsorption mechanisms have been confirmed by solid-state nuclear magnetic resonance (SSNMR). The excellent pollutant removal ability demonstrates the promise of the pillar[5]arene-based 3D network polymer for rapid waste-water treatment.