Uveal melanoma (UM) is a leading intraocular malignancy with a high 5‐year mortality rate, and radiotherapy is the primary approach for UM treatment. However, the elevated lactic acid, deficiency in ROS, and hypoxic tumor microenvironment have severely reduced the radiotherapy outcomes. Hence, this study devised a novel CoMnFe‐layered double oxides (LDO) nanosheet with multienzyme activities for UM radiotherapy enhancement. On one hand, LDO nanozyme can catalyze hydrogen peroxide (H2O2) in the tumor microenvironment into oxygen and reactive oxygen species (ROS), significantly boosting ROS production during radiotherapy. Simultaneously, LDO efficiently scavenged lactic acid, thereby impeding the DNA and protein repair in tumor cells to synergistically enhance the effect of radiotherapy. Moreover, density functional theory (DFT) calculations decoded the transformation pathway from lactic to pyruvic acid, elucidating a previously unexplored facet of nanozyme activity. The introduction of this innovative nanomaterial paves the way for a novel, targeted, and highly effective therapeutic approach, offering new avenues for the management of UM and other cancer types.
6 February 2022 in Materials Science and Engineering: C
The immune response induced by surface topography crucially determines the implant success. However, how the immune response is mediated by the size of surface topography remains unclear. Hence, various biocompatible Mg-Al layered double hydroxides sheet-array films with different sizes (nano, micro and nano/micro mixture) were constructed on the biomedical titanium, and their osteo-immunomodulation effects on the macrophages were explored. The nano-sheet array structures significantly promoted the polarization of M2 macrophages by activating the PI3K-AKT-mTOR signaling pathway with high gene expressions of integrin β2 and FAK. While the micro-sheet array structures enhanced osteogenic differentiation of mouse bone marrow mesenchymal stem cells (mBMSCs) via ROCK-YAP/TAZ-mediated mechanotransduction. Moreover, the nano-sheet array structures promoted the osteogenic differentiation of mBMSCs with a high proportion of M2 macrophages through a shared medium. This study gave further information concerning integrin-induced focal adhesions in cells of different sheet array structures and their role in macrophage polarization and osteogenic differentiation of mBMSCs, which might help to design biomaterial surfaces with optimal geometry for a desired immunemodulation.
Implant-associated infections are urgently addressed; however, existing materials are difficult to kill bacteria without damaging cells. Here, we propose an innovative concept of selective antibacterial starvation therapy based on interfering with proton and electron transfer on the bacterial membrane. As a proof-of-principle demonstration, a special Schottky heterojunction film composed of gold and alkaline magnesium-iron mixed metal oxides (Au/MgFe-MMO) was constructed on the titanium implant. Once bacteria contacted this implant, the Au/MgFe-MMO film continuously captured the proton and electron participated in respiratory chain of bacteria to impede their energy metabolism, leading to the deficit of adenosine 5′-triphosphate. Prolonged exposure to this starvation state inhibited numerous biosynthesis processes and triggered severe oxidative stress in bacteria, ultimately leading to their death due to DNA and membrane damage. In addition, this heterojunction film was comfortable for mammalian cells, without inhibiting mitochondrial function. This proposed starvation antibacterial therapy gives a notable perspective in designing biosafe smart antibacterial biomaterials.
Titanium and its alloys have been widely used for orthopedic and dental implants. However, implant failures often occur due to the implant-related bacterial infections. Herein, titanium oxide nanotubes (TNTs) with an average diameter of 75 nm were formed by anodizing on the surface of titanium, and subsequently gold (Au) nanoparticles were deposited on TNTs by magnetron sputtering (Au@TNTs). The antibacterial study shows that TNTs surface decorated with Au nanoparticles exhibits the preferable effect in restricting the growth of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) even under dark conditions, and the antibacterial rates reached 84% and 75%, respectively. In addition, the constructed film showed no cytotoxicity. Such a selective bactericidal effect of Au@TNTs samples might be attributed to the photocatalytic memory effect, which provides a new insight in the designing of antibacterial surfaces for biomedical application.