Journal of Nanobiotechnology最新文献

Stem cell-derived extracellular vesicles (EVs) have emerged as a safe and potent alternative to regenerative medicine in recent decades. Furthermore, the adjustment of EV functions has been recently enabled by certain stem cell preconditioning methods, providing an exceptional opportunity to enhance the therapeutic potential or confer additional functions of stem cell-derived EVs. In this review, we discuss the recent progress of functionalized EVs, based on stem cell preconditioning, for treating various organ systems, such as the musculoskeletal system, nervous system, integumentary system, cardiovascular system, renal system, and respiratory system. Additionally, we summarize the expected outcomes of preconditioning methods for stem cells and their EVs. With recent progress, we suggest considerations and future directions for developing personalized medicine based on preconditioned stem cell-derived EVs.

Elevated oxidative stress and inflammation, bacterial infections, and vascular impairment undoubtedly impede the normal diabetic wound healing process, which has encouraged the development of high-performance dressings for wound management. Herein, a new type of multiple-crosslinked injectable hydrogel, GCP, was developed via the radical polymerization of propenyl groups and the formation of copper‒polyphenol coordination bonds and Schiff base bonds. The copper‒polyphenol coordination and Schiff base bonds in the GCP hydrogel were disrupted in the acidic microenvironment of diabetic wound, resulting in the release of copper ions and protocatechualdehyde (PA) to scavenge reactive oxygen species (ROS), promote angiogenesis and cell migration, and exert antibacterial and anti-inflammatory activities via the CuPA complexes. Consequently, markedly accelerated infected diabetic wounds healing was achieved through this tissue microenvironment remodeling strategy. Moreover, the underlying mechanism of the antibacterial properties was investigated by 16S rRNA sequencing. The results indicated that the CuPA complexes can clearly inhibit the growth and reproduction of S. aureus by downregulating specific genes associated with ABC transporters, hindering bacterial protein synthesis, and enhancing oxidoreductase activity. This innovative hydrogel platform for wound management may inspire new methods for the preparation of high-performance biomedical materials and the treatment of other clinical diseases.

Circular RNAs (circRNAs), constituting a novel class of endogenous non-coding RNAs generated through the reverse splicing of mRNA precursors, possess the capacity to regulate gene transcription and translation. Recently, the pivotal role of circRNAs in controlling vascular aging, as well as the pathogenesis and progression of aging-related vascular diseases, has garnered substantial attention. Vascular aging plays a crucial role in the increased morbidity and mortality of the elderly. Endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) are crucial components of the intima and media layers of the vascular wall, respectively, and are closely involved in the mechanisms underlying vascular aging and aging-related vascular diseases. The review aims to provide a comprehensive exploration of the connection between circRNAs and vascular aging, as well as aging-related vascular diseases. Besides, circRNAs, as potential diagnostic markers or therapeutic targets for vascular aging and aging-related vascular diseases, will be discussed thoroughly, along with the challenges and limitations of their clinical application. Investigating the role and molecular mechanisms of circRNAs in vascular aging and aging-related vascular diseases will provide a novel insight into early diagnosis and therapy, and even effective prognosis assessment of these conditions.

Background: Deoxynivalenol (DON), a mycotoxin produced by Fusarium species, posed significant threats to food safety and human health due to its widespread prevalence and detrimental effects. Upon exposure, the liver, which played a crucial role in detoxifying DON, experienced depleted antioxidant levels and heightened inflammatory responses. Bone marrow mesenchymal stem cell (BMSC)-derived exosomes (BMSC-exos) exhibited therapeutic potential by promoting cellular repair and delivering bioactive substances, such as cerium dioxide nanoparticles (CeO₂ NPs), which are recognized for their ability to mitigate oxidative stress and inflammation.

Results: We successfully loaded BMSC-exos with CeO₂ NPs (BMSC-exos @ CeO₂) using extrusion techniques, verified through electron microscopy and elemental mapping. The resulting BMSC-exos @ CeO₂ displayed low cytotoxicity, boosted antioxidant activity, and reduced inflammation in Hepa 1-6 cells with DON condition. In vivo study, BMSC-exos @ CeO₂ maintained stability for 72 h, it also can prevent antioxidant depletion and inhibit liver inflammation under the DON condition. After BMSC-exos @ CeO₂ treatment, multi-omics analyses further highlighted significant changes in metabolic and protein signaling pathways, notably in linoleic and arachidonic acid metabolism. Key pathways about AMPK and JAK1/STAT3 were involved in mitigating liver damage with or without DON.

Conclusion: Our findings revealed BMSC-exos @ CeO₂ as a promising therapeutic strategy against DON's toxicity, offering valuable insights into their potential for liver protection.

Acute myocardial infarction (AMI) destroys heart cells by disrupting the oxygen supply. Improving oxygen delivery to the injured area may avoid cell death and regenerate the heart. We present the creation of oxygen-producing injectable bio-macromolecular hydrogels using catalase (CAT) loaded alginate (Alg) and fibrin (Fib) incorporated with the Mesenchymal stem cells (MSCs) derived exosomes (Exo). The composite hydrogel additionally incorporates electrical stimulating qualities from gold nanoparticles (AuNPs). In vitro experiments showed that this composite hydrogel (Exo/Hydro/AuNPs/CAT) exhibits electrical conductivity similar to an actual heart and effectively releases CAT. The O_2-generating hydrogel released oxygen for almost 5 days under hypoxia conditions. We showed that after 7 days of in vitro cell culture, produces the same paracrine factors as rat neonatal cardiomyocytes (RNCs), rat cardiac fibroblasts (RCFs), and Human Umbilical Vein Endothelial Cells (HUVECs), imitating capillary architecture and function. Our work demonstrated that the injectable conductive hydrogel loaded with CAT and AuNPs reduced left ventricular remodeling and myocardial dysfunction in rats after MI. Exo/Hydro/AuNPs/CAT boosted infarct margin angiogenesis, decreased cell apoptosis, and necrosis, and elevated Connexm43 (Cx43) expression. The therapeutic benefits and the ease of production of oxygen make this bioactive injectable conductive hydrogel an effective therapeutic agent for MI.

Elevated copper levels induce tumor cuproptosis and ferroptosis, leading to immunogenic cell death and subsequent antitumor immune responses. However, dysregulated copper metabolism in tumor cells maintains homeostatic copper balance, while hypoxic microenvironments hinder therapeutic efficacy. In this study, we present a nanozyme system, termed CussOMEp, comprising a copper-based nanovector (CussNV) that is PEGylated and loaded with omeprazole, a copper transporter inhibitor, to enhance tumor synergistic immunotherapy by promoting cuproptosis and ferroptosis. CussNV is assembled from dithiodiglycolic acid and copper ions, exhibiting peroxidase, glutathione oxidase, and catalase-like activities, along with responsive degradability. This nanozyme alleviates tumor hypoxia by producing oxygen, induces ferroptosis through the generation of lethal hydroxyl radicals, and depletes glutathione. Additionally, omeprazole increases cellular copper concentration and oxidative stress by inhibiting the intracellular copper-transporting ATPase 1 (ATP7A), enhancing lipoylated protein oligomerization and cuproptosis. In a breast tumor mouse model, CussOMEp elicits robust antitumor immune responses, including dendritic cell maturation and T cell proliferation. When combined with PD-1 antibodies (αPD-1), CussOMEp significantly inhibits tumor metastasis in bilateral and lung metastatic models. This work presents a functional nanozyme system as a promising strategy for synergistic tumor immunotherapy leveraging ferroptosis and cuproptosis.

Nickel-based nanomaterials (NBNs) have seen a surge in usage across a variety of applications. However, the widespread use of NBNs has led to increased human exposure, raising questions about their associated health risks, both in the short and long term. Additionally, the spread of NBNs in the environment has attracted considerable attention, emerging as a vital focus for research and development. This review aims to provide an in-depth assessment of the current understanding of NBNs toxicity, the mechanisms underlying their toxicological effects, and the strategies for mitigating associated health risks. We begin by examining the physicochemical properties of NBNs, such as particle size, composition and surface functionalization, which are key determinants of their biological interactions and toxicity. Then, through an extensive analysis of in vitro and in vivo studies, we highlight the adverse effects of NBNs exposure, including the generation of reactive oxygen species (ROS), oxidative stress, inflammation, cytotoxicity, genotoxicity, and immunotoxicity. To address the potential health risks associated with NBNs, we propose future strategies for risk prevention, including the development of safer nanomaterial designs, implementation of stringent regulatory guidelines, and advancement of novel toxicity testing approaches.

Among nanoparticle platforms, light or photoresponsive nanoparticles have emerged as a promising drug delivery strategy with spatiotemporal control while minimizing off-target effects. The characteristic absorption spectrum of the photoresponsive moiety dictates the wavelength of light needed to activate bond cleavage. However, the low tissue penetration depth limit and short-wavelength ultraviolet (UV) cellular toxicity are considered disadvantageous. This study developed a vestibular ganglion neuron organoid as a model for vestibulopathy. UV and near-infrared (NIR) radiation targeted the inner ear and neural cells, followed by toxicity evaluation. A significantly smaller toxicity of NIR light was confirmed. The photocleavage release of brain-derived neurotrophic factor (BDNF) was used by applying NIR wavelength. The results indicate that polyethylene glycol octamethylene diamine derivative conjugated with leucomethylene blue with an ethanolamine linker nanoparticle can be effectively disassembled and release BDNF when using the 808 nm laser as a trigger. The findings of the cytotoxicity assay suggest that photocleavable nanoparticles (PCNs) and laser irradiation are safe and biocompatible for human-derived and neural progenitor types of cells. Phototriggered BDNF release by NIR laser supported the growth and differentiation of human neural progenitor cells in culture. In addition, the vestibulopathy organoid exhibited a significant regenerative effect. This study harnesses the full potential of NIR laser PCNs to treat vestibular neuropathies.