yfliu15

Herein, we demonstrated that targeted protein upregulation of STING potentiates immunotherapy agents. Using a luminescence-based cellular assay, we discovered a novel protein-protein interaction modulator, SB24011, that inhibited the STING-TRIM29 E3 ligase interaction and upregulated cellular STING levels. As a result, SB24011 boosted STING immunity and improved the in vivo efficacy of immunotherapy with a STING agonist and an anti-PD-1 antibody.

Abstract

Modulating target proteins via the ubiquitin-proteasome system has recently expanded the scope of pharmacological inventions. Stimulator of interferon genes (STING) is an auspicious target for immunotherapy. Seminal studies envisioned the importance of STING as well as the utility of its agonists in immunotherapy outcomes. Herein, we suggest UPPRIS (upregulation of target proteins by protein-protein interaction strategy) to pharmacologically increase cellular STING levels for improved immunotherapy. We discovered the small molecule SB24011 that inhibits STING-TRIM29 E3 ligase interaction, thus blocking TRIM29-induced degradation of STING. SB24011 enhanced STING immunity by upregulating STING protein levels, which robustly potentiated the immunotherapy efficacy of STING agonist and anti-PD-1 antibody via systemic anticancer immunity. Overall, we demonstrated that targeted protein upregulation of STING can be a promising approach for immuno-oncology.

Visible-light-induced photocatalytic CO₂ reduction in aqueous media was achieved with amphiphilic polycarbonate micellar rhenium catalysts. Coordination polymers were prepared comprising amphiphilic micelles with tunable solubility in water. By adjusting the proportion of hydrophilic and hydrophobic segments, the photocatalytic system was tailored to select for CO evolution.

Abstract

A triblock amphiphilic polymer derived from the copolymerization of CO₂ and epoxides containing a bipyridine rhenium complex in its backbone is shown to effectively catalyze the visible-light-driven reduction of CO₂ to CO. This polymer provides uniformly spherical micelles in aqueous solution, where the metal catalyst is sequestered in the hydrophobic portion of the nanostructured micelle. CO₂ to CO reduction occurs in an efficient visible-light-driven process in aqueous media with turnover numbers up to 110 (>99 % selectivity) in the absence of a photosensitizer, which is a 37-fold enhancement over the corresponding molecular rhenium catalyst in organic solvent. Notably, the amphiphilic polycarbonate micelle rhenium catalyst suppresses H₂ generation, presumably by preventing deactivation of the active catalytic center by water.

DNA framework-based programmable atom-like nanoparticles (aptPANs) and their assemblies with fixed aptamer copy numbers but different directionality were designed. These are employed to direct multivalent aptamer–receptor binding on the cell membrane interface. The directional-yet-flexible aptPAN molecules exhibit the adaptability to the receptor distribution on cell surfaces and thus high affinity against target tumor cells.

Abstract

Multivalent interactions of biomolecules play pivotal roles in physiological and pathological settings. Whereas the directionality of the interactions is crucial, the state-of-the-art synthetic multivalent ligand–receptor systems generally lack programmable approaches for orthogonal directionality. Here, we report the design of programmable atom-like nanoparticles (aptPANs) to direct multivalent aptamer–receptor binding on the cell interface. The positions of the aptamer motifs can be prescribed on tetrahedral DNA frameworks to realize atom-like orthogonal valence and direction, enabling the construction of multivalent molecules with fixed aptamer copy numbers but different directionality. These directional-yet-flexible aptPAN molecules exhibit the adaptability to the receptor distribution on cell surfaces. We demonstrate the high-affinity tumor cell binding with a linear aptPAN oligomer (≈13-fold improved compared to free aptamers), which leads to ≈50 % suppression of cell growth.

Metasurfaces based on disordered arrangements of silicon nanoresonators are used to implement wavelength-selective optical diffusers with nearly Lambertian scattering profiles and a high tolerance for incidence angles and polarizations. Their working principles and scattering performances are discussed on the basis of exhaustive experimental and numerical studies. Such diffusers open new opportunities in applications like fluorescence microscopy, augmented reality displays, or wavefront-shaping.

Abstract

Conventional optical diffusers, such as thick volume scatterers (Rayleigh scattering) or microstructured surface scatterers (geometric scattering), lack the potential for on-chip integration and are thus incompatible with next-generation photonic devices. Dielectric Huygens’ metasurfaces, on the other hand, consist of 2D arrangements of resonant dielectric nanoparticles and therefore constitute a promising material platform for ultrathin and highly efficient photonic devices. When the nanoparticles are arranged in a random but statistically specific fashion, diffusers with exceptional properties are expected to come within reach. This work explores how dielectric Huygens’ metasurfaces can implement wavelength-selective diffusers with negligible absorption losses and nearly Lambertian scattering profiles that are largely independent of the angle and polarization of incident waves. The combination of tailored positional disorder with a carefully balanced electric and magnetic response of the nanoparticles is shown to be an integral requirement for the operation as a diffuser. The proposed metasurfaces’ directional scattering performance is characterized both experimentally and numerically, and their usability in wavefront-shaping applications is highlighted. Since the metasurfaces operate on the principles of Mie scattering and are embedded in a glassy environment, they may easily be incorporated in integrated photonic devices, fiber optics, or mechanically robust augmented reality displays.

Nature Photonics, Published online: 09 September 2021; doi:10.1038/s41566-021-00862-3

Strong lanthanide-doped upconversion luminescence enhancement is achieved by the use of surface molecules which enhance four-photon upconversion emission. The results may lead to new, highly emissive, nanohybrid systems.