Nanotechnology has played an important role in drug delivery and biomedical imaging over the past two decades. In particular, nanoscale metal-organic frameworks (nMOFs) are emerging as an important class of biomedically relevant nanomaterials due to their high porosity, multifunctionality, and biocompatibility. The high porosity of nMOFs allows for the encapsulation of exceptionally high payloads of therapeutic and/or imaging cargoes while the building blocks-both ligands and the secondary building units (SBUs)-can be utilized to load drugs and/or imaging agents via covalent attachment. The ligands and SBUs of nMOFs can also be functionalized for surface passivation or active targeting at overexpressed biomarkers. The metal ions or metal clusters on nMOFs also render them viable candidates as contrast agents for magnetic resonance imaging, computed tomography, or other imaging modalities. This review article summarizes recent progress on nMOF designs and their exploration in biomedical areas. First, the therapeutic applications of nMOFs, based on four distinct drug loading strategies, are discussed, followed by a summary of nMOF designs for imaging and biosensing. The review is concluded by exploring the fundamental challenges facing nMOF-based therapeutic, imaging, and biosensing agents. This review hopefully can stimulate interdisciplinary research at the intersection of MOFs and biomedicine.

Checkpoint blockade immunotherapy enhances systemic antitumor immune response by targeting T cell inhibitory pathways; however, inadequate T cell infiltration has limited its anticancer efficacy. Radiotherapy (RT) has local immunomodulatory effects that can alter the microenvironment of irradiated tumors to synergize with immune checkpoint blockade. However, even with high doses of radiation, RT has rarely elicited systemic immune responses. Herein, we report the design of two porous Hf-based nanoscale metal-organic frameworks (nMOFs) as highly effective radioenhancers that significantly outperform HfO2, a clinically investigated radioenhancer in vitro and in vivo. Importantly, the combination of nMOF-mediated low-dose RT with an anti-programmed death-ligand 1 antibody effectively extends the local therapeutic effects of RT to distant tumors via abscopal effects. Our work establishes the feasibility of combining nMOF-mediated RT with immune checkpoint blockade to elicit systemic antitumor immunity in non-T cell-inflamed tumor phenotypes without normal tissue toxicity, promising to broaden the application of checkpoint blockade immunotherapy.

The authors report the use of nanoscale metal-organic framework (nMOF) to deliver Cu 2+ ions and porphyrins for estradiol-induced chemodynamic therapy and light-driven photodynamic therapy, respectively, to achieve local tumor control. The combination of nMOF-mediated radical therapy with anti-PD-L1 immunotherapy systemically rejects distant tumors via abscopal effects in a melanoma mouse model.

An inexpensive and commercially available ultraviolet light device, intended for “drying” gel-type fingernail polish, was tested as a photochemical reactor with five organic photochemical laboratory experiments. The device performs satisfactorily and gives product yields comparable to or better than reported results, often in less time. The low cost and ease of use should make photochemical reactions more accessible to undergraduate students.

RcsB is a highly conserved transcription regulator of the Rcs phosphorelay system, a complex two-component signal transduction system (N. Majdalani and S. Gottesman, Annu Rev Microbiol 59:379–405, 2005; A. J. Wolfe, Curr Opin Microbiol 13:204–209, 2010, https://doi.org/10.1016/j.mib.2010.01.002; D. J. Clarke, Future Microbiol 5:1173–1184, 2010, https://doi.org/10.2217/fmb.10.83). RcsB plays an important role in virulence and pathogenicity in human hosts by regulating biofilm formation. RcsB can regulate transcription alone or together with its auxiliary transcription regulators by forming heterodimers. This complexity allows RcsB to regulate transcription of more than 600 bacterial genes in response to different stresses (D. Wang et al., Mol Plant Microbe Interact 25:6–17, 2012, https://doi.org/10.1094/MPMI-08-11-0207). Despite increasing knowledge of RcsB importance, molecular mechanisms that drive the ability of RcsB to control transcription of a large number of genes remain unclear. Here, we present crystal structures of unphosphorylated RcsB in complex with the consensus DNA-binding sequence of 22-mer (DNA22) and 18-mer (DNA18) of the flhDC operon from Escherichia coli determined at 3.15- and 3.37-Å resolution, respectively. The results of our structural analysis combined with the results of in vitro binding assays provide valuable insights to the protein regulatory mechanism, demonstrate how RcsB recognizes target DNA sequences, and reveal a unique oligomeric state that allows RcsB to form homo- and heterodimers. This information will help us understand the complex mechanisms of transcriptional regulation by RcsB in bacteria.