Biodegradable and Efficient Charge-Migrated Z-Scheme Heterojunction Amplifies Cancer Ferroptosis by Blocking Defensive Redox System.

Ferroptosis is an emerging non-apoptotic death process, mainly involving lipid peroxidation (LPO) caused by iron accumulation, which is potentially lethal to the intrinsically apoptotic-resistant malignant tumor. However, it is still restricted by the inherent antioxidant systems of tumor cells and the poor efficacy of traditional iron-based ferroptosis initiators. Herein, the study develops a novel ferroptosis-inducing agent based on PEGylated Cu+/Cu2+-doped black phosphorus@polypyrrole heterojunction (BP@CPP), which is constructed by utilizing the phosphate on the surface of BP to chelate Cu ions and initiating subsequent in situ polymerization of pyrrole. As a novel Z-scheme heterojunction, BP@CPP possesses an excellent photocatalytic activity in which the separated electron-hole pairs under laser irradiation endow it with powerful oxidizing and reducing capacities, which synergy with Cu+/Cu2+ self-cycling catalyzing Fenton-like reaction to further strengthen reactive oxygen species (ROS) accumulation, glutathione (GSH) depletion, and glutathione peroxidase 4 (GPX4) inactivation, ultimately leading to efficient ferroptosis. Systematic in vitro and in vivo evaluations demonstrate that BP@CPP effectively inhibit tumor growth by inducing desired ferroptosis while maintaining a favorable biosafety in the body. Therefore, the developed BP@CPP-based ferroptosis initiator provides a promising strategy for ferroptosis-like cancer therapy.

Curcumin Attenuates Periodontal Injury via Inhibiting Ferroptosis of Ligature-Induced Periodontitis in Mice.

Periodontitis is a chronic infectious disease characterized by the destruction of connective tissue and alveolar bone that eventually leads to tooth loss. Ferroptosis is an iron-dependent regulated cell death and is involved in ligature-induced periodontitis in vivo. Studies have demonstrated that curcumin has a potential therapeutic effect on periodontitis, but the mechanism is still unclear. The purpose of this study was to investigate the protective effects of curcumin on alleviating ferroptosis in periodontitis. Ligature-induced periodontal-diseased mice were used to detect the protective effect of curcumin. The level of superoxide dismutase (SOD), malondialdehyde (MDA) and total glutathione (GSH) in gingiva and alveolar bone were assayed. Furthermore, the mRNA expression levels of acsl4, slc7a11, gpx4 and tfr1 were measured using qPCR and the protein expression of ACSL4, SLC7A11, GPX4 and TfR1 were investigated by Western blot and immunocytochemistry (IHC). Curcumin reduced the level of MDA and increased the level of GSH. Additionally, curcumin was proven to significantly increase the expression levels of SLC7A11 and GPX4 and inhibit the expression of ACSL4 and TfR1. In conclusion, curcumin plays a protective role by inhibiting ferroptosis in ligature-induced periodontal-diseased mice.

A potential bilayer skin substitute based on electrospun silk-elastin-like protein nanofiber membrane covered with bacterial cellulose.

Skin substitutes are designed to promote wound healing by replacing extracellular matrix. Silk-elastin-like protein is a renewable extracellular matrix-like material that integrated the advantages of silk and elastin-like protein. In this study, electrospun silk-elastin-like protein (SELP) nanofiber membrane covered with bacterial cellulose (BC) was created as a potential skin substitute to mimic gradient structure of epidermis and dermis of skin. The two layers were glued together using adhesive SELP containing 3,4-dihydroxyphenylalanine (DOPA) converted from tyrosine by tyrosinase. Skin topical drugs commonly used in clinical practice can penetrate through the SELP/BC barrier, and the rate of penetration is proportional to drug concentration. BC with dense fibrous structure can act as a barrier to preserve the inner SELP layer and prevent bacterial invasion, with a blocking permeation efficiency over 99% against four species of bacteria. Cell experiments demonstrated that the reticular fibers of SELP could provide an appropriate growth environment for skin cells proliferation and adhesion, which is considered to promote tissue repair and regeneration. The promising results support this strategy to fabricate a silk-elastin-like protein-based biomaterial for skin substitutes in the clinical treatment of full skin injuries and ulcers.

Polystyrene Nanoplastics Activate Autophagy and Suppress Trophoblast Cell Migration/Invasion and Migrasome Formation to Induce Miscarriage.

Nanoplastics (NPs), as emerging pollutants, have attracted global attention. Nevertheless, the adverse effects of NPs on female reproductive health, especially unexplained miscarriage, are poorly understood. Defects of trophoblast cell migration and invasion are associated with miscarriage. Migrasomes were identified as cellular organelles with largely unidentified functions. Whether NPs might affect migration, invasion, and migrasome formation and induce miscarriage has been completely unexplored. In this study, we selected polystyrene nanoplastics (PS-NPs, 50 nm) as a model of plastic particles and treated human trophoblast cells and pregnant mice with PS-NPs at doses near the actual environmental exposure doses of plastic particles in humans. We found that exposure to PS-NPs induced a pregnant mouse miscarriage. PS-NPs suppressed ROCK1-mediated migration/invasion and migrasome formation. SOX2 was identified as the transcription factor of ROCK1. PS-NPs activated autophagy and promoted the autophagy degradation of SOX2, thus suppressing SOX2-mediated ROCK1 transcription. Supplementing with murine SOX2 or ROCK1 could efficiently rescue migration/invasion and migrasome formation and alleviate miscarriage. Analysis of the protein levels of SOX2, ROCK1, TSPAN4, NDST1, P62, and LC-3BII/I in PS-NP-exposed trophoblast cells, villous tissues of unexplained miscarriage patients, and placental tissues of PS-NP-exposed mice gave consistent results. Collectively, this study revealed the reproductive toxicity of nanoplastics and their potential regulatory mechanism, indicating that NP exposure is a risk factor for female reproductive health.

Laccase-mediated formation of hydrogels based on silk-elastin-like protein polymers with ultra-high molecular weight.

As artificial extracellular matrix-like materials, silk-elastin-like protein (SELP) hydrogels, with excellent mechanical properties, high tunability, favorable biocompatibility, and controlled degradability, have become an important candidate in biomedical materials. In this study, SELP is composed of silk-like (GAGAGS) and elastin-like (GXGVP) tandem repeats, in which X residues are set as tyrosine and lysine. Furthermore, SELP polymers are prepared via SpyTag/SpyCatcher. To explore a gentler and more efficient enzymatic crosslinking method, an innovative method was invented to apply laccase to catalyze the formation of SELP hydrogels. Gelation could be successfully achieved in 2-5 min . SELP hydrogels mediated by laccase had the characteristic of low swelling rate, which could maintain a relatively stable shape even when immersed in water, and hence had the potential to be further developed into injectable biomaterials. Additionally, SELP hydrogels cross-linked by laccase showed excellent biocompatibility verified by L929 and HEK 293 T cells with cell viability >93.8 %. SELP hydrogels also exhibit good properties in sustained drug release and cell encapsulation in vitro. This study demonstrates a novel method to construct SELP hydrogels with excellent biocompatibility and expands the possibility of SELP-based material applications in biomedical fields.

Amino-functionalized mesoporous bioactive glass for drug delivery.

An amino-functionalized mesoporous bioactive glass (N-MBG) with a high drug loading capacity and longer drug release time was successfully prepared by using 3-aminopropyltriethoxysilane (APTES) in a short-time chemical reaction. The drug release performance of an MBG and the N-MBG were studied by loading gentamicin sulfate (GS) in a simulated body fluid solution. The results showed that the surface area of the N-MBG increases to 355.01 m2 g-1 after amination at 80 °C for 1 h compared with that of the MBG (288.07 m2 g-1). Meanwhile, the surface zeta-potential of the N-MBG charges from the original negative charge (-10.06 mV) to the positive charge (+5.30 mV). Furthermore, the GS loading rate of the N-MBG is up to 62.92 ± 2.02%, higher than that of the MBG (48.90 ± 1.71%). In addition, the N-MBG has a longer drug release period and the seven-day accumulative release from the N-MBG reached only 45.9 ± 1.8%, significantly lower than that of the MBG, 60.7 ± 2.3%. In vitro bioactivity tests suggested that the N-MBG exhibited good biological activity. In conclusion, the N-MBG with a higher loading capacity and longer drug release time can serve as a promising candidate as a drug carrier.