Inclusion Removal Process of Homogeneous CuCr50 Alloy In-Situ Synthesized by Al-Mg Composite Strengthening Reduction Coupling Slagging.

To overcome the problem of Cr2O3 and Al2O3 inclusions in CuCr50 alloy prepared by aluminothermic reduction method, in this paper, a novel methodology for strengthening metal-slag separation through in situ slagging is proposed. CuCr50 alloys were prepared by metallothermic reduction using Al and Al-Mg as reducing agents, and the physical properties of the slag, such as viscosity, density, and surface tension, were adjusted by controlling the proportion of CaO in the slagging agent in the raw material to achieve good separation of the slag-metal. The results show that with the ratio of CaO increased, CaO and MgO were coupled to make slag, which combined with Cr2O3 and Al2O3 to form CaCr2O4, MgCr2O4, and CaAl4O7 in the slag, thus reducing the content of impurities in the alloy. When RCaO/(CaO + Al2O3 + MgO) = 20%, the Cr content ranged from 46.61% to 47.09%, the inclusions accounted for 1.60%, the Cr particle size was refined to 20 µm, the number of Cr spherical crystals accounted for 9.88%, the conductivity reached 14.96 MS/m, and the hardness reached 100.23 HB. After heat treatment, the Cr phase was refined in the alloy, the conductivity increased from 14.96 MS/m to 18.27 MS/m, and the hardness increased from 100.23 HB to 103.1 HB. This method is expected to provide an effective method for the preparation of CuCr50 contact materials.

Mild phototherapy mediated by IR780-Gd-OPN nanomicelles suppresses atherosclerotic plaque progression through the activation of the HSP27-regulated NF-κB pathway.

Reducing plaque lipid content and enhancing plaque stability without causing extensive apoptosis of foam cells are ideal requirements for developing a safe and effective treatment of atherosclerosis. In this study, we synthesized IR780-Gd-OPN nanomicelles by conjugating osteopontin (OPN) and loading a gadolinium-macrocyclic ligand (Gd-DOTA) onto near-infrared dye IR780-polyethylene glycol polymer. The nanomicelles were employed for mild phototherapy of atherosclerotic plaques and dual-mode imaging with near-infrared fluorescence and magnetic resonance. In vitro results reveal that the mild phototherapy mediated by IR780-Gd-OPN nanomicelles not only activates heat shock protein (HSP) 27 to protect foam cells against apoptosis but also inhibits the nuclear factor kappa-B (NF-κB) pathway to regulate lipid metabolism and macrophage polarization, thereby diminishing the inflammatory response. In vivo results further validate that mild phototherapy effectively reduces plaque lipid content and size while simultaneously enhancing plaque stability by regulating the ratio of M1 and M2-type macrophages. In summary, this study presents a promising approach for developing a safe and highly efficient method for the precise therapeutic visualization of atherosclerosis. STATEMENT OF SIGNIFICANCE: The rupture of unstable atherosclerotic plaques is a major cause of high mortality rates in cardiovascular diseases. Therefore, the ideal outcome of atherosclerosis treatment is to reduce plaque size while enhancing plaque stability. To address this challenge, we designed IR780-Gd-OPN nanomicelles for mild phototherapy of atherosclerosis. This treatment can effectively reduce plaque size while significantly improving plaque stability by increasing collagen fiber content and elevating the ratio of M2/M1 macrophages, which is mainly attributed to the inhibition of the NF-κB signaling pathway by mild phototherapy-activated HSP27. In summary, our proposed mild phototherapy strategy provides a promising approach for safe and effective treatment of atherosclerosis.

Two-dimensional peptide nanosheets functionalized with gold nanorods for photothermal therapy of tumors.

Self-assembled peptide nanomaterials exhibit great potential for applications in materials science, energy storage, nanodevices, analytical science, biomedicine, tissue engineering, and others due to their tailorable ordered nanostructures and unique physical, chemical, and biological properties. Although one-dimensional peptide nanofibers and nanotubes have been widely used for biomedical applications, the design and synthesis of two-dimensional (2D) peptide nanostructures for cancer therapy remain challenging. In this work, we describe the creation of 2D biocompatible peptide nanosheets (PNSs) through molecular self-assembly, which can provide support matrixes for conjugating gold nanorods (AuNRs) to form high-performance 2D nanomaterials for photothermal conversion. After molecular modification, AuNRs can be chemically conjugated onto the surface of 2D PNSs, and the created PNS-AuNR nanohybrids serve as a potential nanoplatform for photothermal therapy of tumor cells. The obtained results indicate that both PNSs and AuNRs contribute to the improved efficiency of photothermal therapy (PTT) of tumors, in which 2D PNSs provide high biocompatibility and a large surface area for binding AuNRs, and AuNRs show a high PTT ability towards tumors. The strategies of molecular design and functional tailoring of self-assembled peptide nanomaterials shown in this study are valuable and inspire the synthesis of biomimetic nanomaterials for biomedicine and tissue engineering applications.

Polydopamine nanoparticle-mediated mild photothermal therapy for inhibiting atherosclerotic plaque progression by regulating lipid metabolism of foam cells.

Since apoptosis of foam, cells can induce plaque instability, reducing intracellular lipid content while protecting foam cells from apoptosis is beneficial for the safe and efficient therapy of atherosclerosis. In this study, osteopontin-coupled polydopamine (PDA-OPN) nanoparticles were synthesized and applied to target mild photothermal therapy (PTT) of atherosclerosis. The results from laser confocal microscopy indicate that PDA-OPN nanoparticles can be specially recognized and absorbed by foam cells. Under near-infrared laser irradiation, the mild photothermal generated by PDA-OPN decreases intracellular lipid accumulation but does not induce cell apoptosis. In vivo treatments demonstrate that mild PTT can substantially reduce plaque area and improve plaque stability by upregulating the expression of plaque fibrosis in ApoE-/- mice. Our findings reinforce that the PDA-OPN nanoparticle-mediated mild PTT can inhibit atherosclerotic progression, which provides new insights for developing safe and effective treatment methods for atherosclerosis.

Advances in imaging and treatment of atherosclerosis based on organic nanoparticles.

Atherosclerosis, a systemic chronic inflammatory disease, can lead to thrombosis and vascular occlusion, thereby inducing a series of serious vascular diseases. Currently, distinguishing unstable plaques early and achieving more effective treatment are the two main clinical concerns in atherosclerosis. Organic nanoparticles have great potential in atherosclerotic imaging and treatment, showing superior biocompatibility, drug-loading capacity, and synthesis. This article illustrates the process of atherosclerosis onset and the key targeted cells, then systematically summarizes recent progress made in organic nanoparticle-based imaging of different types of targeted cells and therapeutic methods for atherosclerosis, including optical and acoustic-induced therapy, drug delivery, gene therapy, and immunotherapy. Finally, we discuss the major impediments that need to be addressed in future clinical practice. We believe this article will help readers to develop a comprehensive and in-depth understanding of organic nanoparticle-based atherosclerotic imaging and treatment, thus advancing further development of anti-atherosclerosis therapies.

Black TiO2 nanoprobe-mediated mild phototherapy reduces intracellular lipid levels in atherosclerotic foam cells via cholesterol regulation pathways instead of apoptosis.

Given that apoptosis increases the risk of plaque rupture, strategies that reduce intracellular lipid levels without killing foam cells are warranted for safe and effective treatment of atherosclerosis. In this study, a mild phototherapy strategy is carried out to achieve the hypothesis. Foam cell-targeted nanoprobes that allow photothermal therapy (PTT) and/or photodynamic therapy (PDT) were prepared by loading hyaluronan and porphine onto black TiO2 nanoparticles. The results showed that when temperatures below 45 °C, PTT alone and PTT + PDT significantly reduced the intracellular lipid burden without inducing evidently apoptosis or necrosis. In contrast, the use of PDT alone resulted in only a slight reduction in lipid levels and induced massive apoptosis or necrosis. The protective effect against apoptosis or necrosis after mild-temperature PTT and PTT + PDT was correlated with the upregulation of heat shock protein 27. Further, mild-temperature PTT and PTT + PDT attenuated intracellular cholesterol biosynthesis and excess cholesterol uptake via the SREBP2/LDLR pathway, and also triggered ABCA1-mediated cholesterol efflux, ultimately inhibiting lipid accumulation in foam cells. Our results offer new insights into the mechanism of lipid regulation in foam cells and indicate that the black TiO2 nanoprobes could allow safer and more effective phototherapy of atherosclerosis.