Improved Imaging Surface for Quantitative Single-Molecule Microscopy.

Preventing nonspecific binding is essential for sensitive surface-based quantitative single-molecule microscopy. Here we report a much-simplified RainX-F127 (RF-127) surface with improved passivation. This surface achieves up to 100-fold less nonspecific binding from protein aggregates compared to commonly used polyethylene glycol (PEG) surfaces. The method is compatible with common single-molecule techniques including single-molecule pull-down (SiMPull), super-resolution imaging, antibody-binding screening and single exosome visualization. This method is also able to specifically detect alpha-synuclein (α-syn) and tau aggregates from a wide range of biofluids including human serum, brain extracts, cerebrospinal fluid (CSF) and saliva. The simplicity of this method further allows the functionalization of microplates for robot-assisted high-throughput single-molecule experiments. Overall, this simple but improved surface offers a versatile platform for quantitative single-molecule microscopy without the need for specialized equipment or personnel.

Ultracompact Nanotheranostic PEG Platform for Cancer Applications.

We present a new targetable nanoconstruct (NC) capable of simultaneously serving as a therapeutic platform for photodynamic therapy (PDT) as well as a magnetic resonance (MR) molecular imaging agent, free of heavy metal atoms. PDT has seen much interest with the introduction of NC-assisted cell-specific targeting of the photosensitizer (PS). The previously reported ultrasmall 8-arm polyethylene glycol amine (8PEGA) NC, with an attached chlorin e6 (Ce6) PS, yielded promising results for PDT of heart arrhythmia, in vivo and ex vivo, on live rat and sheep hearts, respectively, when using targeting peptides for cell-specific ablation of cardio-myocytes. Here we explore the extension of this NC-based PDT to cancer. For this purpose, we switched the targeting peptide from CTP-cys to F3-cys. Notably, the 8PEGA-Ce6 NCs have a superior reactive oxygen species (ROS) production compared to traditional Ce6 encapsulated polyacrylamide (PAAm) NCs, which should be advantageous for PDT. This NC is also cyto-compatible and offers chemical flexibility for the attachment of a choice of targeting peptides. Finally, this label-free 8PEGA NC can be directly and selectively imaged by MRI, using standard spin-echo imaging sequences with large diffusion magnetic field gradients to suppress the water signal. Notably, due to its ultrasmall size this NC is also expected to have improved in vivo penetration and bioelimination, as was already shown in previous biodistribution studies.

Synthesis of bimetallic uranium and neptunium complexes of a binucleating macrocycle and determination of the solid-state structure by magnetic analysis.

Syntheses of the bimetallic uranium(III) and neptunium(III) complexes [(UI)(2)(L)], [(NpI)(2)(L)], and [{U(BH(4))}(2)(L)] of the Schiff-base pyrrole macrocycles L are described. In the absence of single-crystal structural data, fitting of the variable-temperature solid-state magnetic data allows the prediction of polymeric structures for these compounds in the solid state.

Constructing cerium supramolecular wheels and encapsulating uranium with a Schiff-base calixpyrrole ligand.

Trinuclear, supramolecular wheel structures are formed spontaneously from the metallation of a Schiff-base-pyrrole macrocycle by Ce(3+) cations, while the related actinide U(3+) cation is instead oxidised to U(4+) and encapsulated by the macrocyclic framework.