Rod-Shaped Mesoporous Zinc-Containing Bioactive Glass Nanoparticles: Structural, Physico-Chemical, Antioxidant, and Immuno-Regulation Properties.

Bioactive glass nanoparticles (BGNs) are applied widely in tissue regeneration. Varied micro/nanostructures and components of BGNs have been designed for different applications. In the present study, nanorod-shaped mesoporous zinc-containing bioactive glass nanoparticles (ZnRBGNs) were designed and developed to form the bioactive content of composite materials for hard/soft tissue repair and regeneration. The nanostructure and components of the ZnRBGNs were characterized, as were their cytocompatibility and radical-scavenging activity in the presence/absence of cells and their ability to modulate macrophage polarization. The ZnRBGNs possessed a uniform rod shape (length ≈ 500 nm; width ≈ 150 nm) with a mesoporous structure (diameter ≈ 2.4 nm). The leaching liquid of the nanorods at a concentration below 0.5 mg/mL resulted in no cytotoxicity. More significant improvements in the antioxidant and M1-polarization-inhibiting effects and the promotion of M2 polarization were found when culturing the cells with the ZnRBGNs compared to when culturing them with the RBGNs. The doping of the Zn element in RBGNs may lead to improved antioxidant and anti-inflammatory effects, which may be beneficial in tissue regeneration/repair.

Insights into the tolerant function of VWA proteins in terms of expression analysis and RGLG5-VWA crystal structure.

The VWA domain commonly functions as a crucial component of multiprotein complexes, facilitating protein-protein interactions. However, limited studies have focused on the systemic study of VWA proteins in plants. Here, we identified 28 VWA protein genes in Arabidopsis thaliana, categorized into three clades, with one tandem duplication event and four paralogous genes within collinearity blocks. Then, we determined their expression patterns under abiotic stresses by transcriptomic analysis. All five RGLG genes were found to be responsive to at least one kind of abiotic stress, and RGLG5 was identified as a multiple stress-responsive gene, coding an E3 ubiquitin ligase with a VWA domain and a C-terminal RING domain. Subsequently, we explored tolerant function of RGLG5 by determining the crystal structure of its VWA domain. The structural comparison revealed the allosteric regulation mechanism of RGLG5-VWA, wherein the deflection of α7 led to displacement of key residue binding metal ion within MIDAS motif. Our findings provide full-scale knowledge on VWA proteins, and insights into tolerant function of RGLG5-VWA in terms of crystal structure.

Carboxyl-Modified Quantum Dots for NIR-IIb Bone Marrow Imaging.

Real-time, noninvasive, and nonradiative bone imaging can directly visualize bone health but requires bone-targeted probes with high specificity. Herein, we propose that carboxyl-rich fluorescent nanoprobes are easily absorbed by macrophages in bone marrow during circulation, enabling optical bone marrow imaging in vivo. We used PbS/CdS core-shell quantum dots with NIR-IIb (1500-1700 nm) emission as substrates to prepare the carboxyl-rich nanoprobe. In vivo NIR-IIb fluorescence imaging with the nanoprobes showed high resolution and penetration depth in bone tissues and allowed for imaging-guided fracture diagnosis. Bone tissue slices showed substantial accumulation of carboxyl nanoprobes in the bone marrow and strong colocalization with macrophages. Similar results with CdSe quantum dots and an organic nanofluorophore suggest that carboxyl surface modification is effective to achieve bone marrow targeting, providing a novel strategy for developing bone/bone marrow imaging probes.

NIR-II Emissive Superoxide Radical Photogenerator for Photothermal/Photodynamic Therapy against Hypoxic Tumor.

Due to the "Achilles' heels" of hypoxia, complicated location in solid tumor, small molecular photosensitizers with second near-infrared window (NIR-II) fluorescence, type-I photodynamic therapy (PDT), and photothermal therapy (PTT) have attracted great attention. However, these photosensitizers are still few but yet challenging. Herein, an "all in one" NIR-II acceptor-donor-acceptor fused-ring photosensitizer, Y6-Th, is presented for the in-depth diagnosis and efficient treatment of cancer. Benefiting from the strong intramolecular charge transfer, promoted highly efficient intersystem crossing, largely p-conjugated fused-ring structure, and reduced planarity, the fabricated nanoparticles (Y6-Th nanoparticles) can emit NIR-II fluorescence with the peak located at 1020 nm, exclusively generate O2•- for type-I PDT, and display excellent PTT performance under an 808 nm laser stimulation. These characteristics make Y6-Th a distinguished NIR-wavelength-triggered phototheranostic agent, which can effectively therapy the hypoxic tumor using NIR-II-fluorescence-guided type-I PDT/PTT. This work provides a valuable guideline for fabricating high-performing NIR-II emissive superoxide radical photogenerators.