Aerobic vaginitis (AV) is characterized by an abnormal vaginal microbiome accompanied by increased inflammatory responses, and well-known to be associated with high risk of preterm delivery. Local therapy offers a simple manner for the targeted treatment of AV, and nevertheless, the treatment effect is not satisfactory due to various factors. Herein, we present a novel sprayable nanozyme dressing with high anti-microbial and anti-inflammation capabilities for AV treatment, which is proved to improve pregnancy outcomes. The dressing is constituted of nanoenzyme, gelatin and nano-chitosan gel, which can be conveniently administrated in the form of a dry powder and formulate a dense hydrogel barrier at the site of action. Due to the natural characteristics of nano-chitosan, it can be electrostatically adsorbed on the surface of bacterial biofilm for sterilization, so viscous hydrogels have inherent antibacterial activity. The cerium oxide nanozyme wrapped in this dressing possesses the multiple enzyme-like properties with outstanding free radical scavenging activity and anti-inflammatory effects. It is worth mentioning that this dressing has shown significant therapeutic effects in the practical performances of AV mice. The dressing exhibited the significant anti-microbial effects, suggesting its high activity even in acidic environment. Moreover, the inflammatory responses are alleviated by promoted tissue repair, reduced proinflammatory cytokines and modulation of vaginal microbiome. More importantly, the treated mice displayed the restored reproductive function and the increased pregnancy rate. These results indicated that the present sprayable nanozyme dressing may be an ideal candidate for local therapy of AV as well as other gynecological diseases.
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Open Access
Review Article
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Metabolic diseases have emerged as a paramount global health threat amidst evolving lifestyles, with mechanistic investigations and therapeutic advancements impeded by the absence of physiologically relevant human experimental models. Organoids, self-organizing three-dimensional cultures of self-renewing cells, recapitulate in vivo tissue architecture and function by spontaneously forming structures analogous to native organs. Notably, this technology has demonstrated transformative utility across diverse biomedical fields, including disease modeling, developmental biology, regenerative medicine, and precision oncology, garnering substantial attention as a next-generation biological platform. In this review, we summarize recent progress in organoid-based metabolic monitoring and the generation of metabolic disease-associated organoids, detailing their construction methodologies and research milestones. We further discuss the current challenges and the future opportunities of the development and application of organoid technology in metabolic research.
Open Access
Research Article
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Modern therapeutics have substantially advanced for autoimmune disease treatment, however, these drugs are often associated with substantial adverse effects and safety concerns. Thus, there is considerable interest in the development of new treatment strategies. In the present study, apoptotic bodies derived from neutrophil-like cells (Neu-ABs) were employed as a novel modality for autoimmune disease treatment. Neu-ABs were enriched in immunomodulatory protein associated with the polarization of M2 macrophages, which were taken up by macrophages. Efferocytosis of Neu-ABs induced the polarization of macrophages toward the M2 phenotype and increased the secretion of anti-inflammatory mediators in vitro. In collagen-induced arthritis and dextran sulfate sodium-induced ulcerative colitis mouse models, Neu-ABs accumulated in the inflamed tissues. The macrophages in the inflamed tissues phagocytose the Neu-ABs and then exhibit a cascade of anti-inflammatory events via macrophage phenotype regulation in vivo. The therapeutic efficiency of Neu-ABs for rheumatoid arthritis and ulcerative colitis was comparable to their corresponding clinical medication. Still, Neu-ABs exhibited good biological safety. These findings indicate a polarization effect of Neu-ABs for macrophages and highlight the potential of Neu-ABs for autoimmune disease treatment.
Precise clinical treatment of triple-negative breast cancer (TNBC) is an obstacle in clinic. Nanotechnology-assisted photothermal therapy (PTT) is a superior treatment modality for TNBC in terms of precision. However, thermoresistance arising from PTT and insufficient drug release from nanocarriers decrease the efficacy of PTT. AT13387 is a novel HSP90 inhibitor that can weaken thermoresistance and undergoing clinic II phase study, showing satisfactory antitumour activity through molecularly targeted therapy (MTT). Whereas, it has poor solubility. Hence hyaluronic acid and stearic acid were connected by hydrazone bonds and disulfide bonds, forming an amphipathic copolymer that could self-assembled into nanomicelles, followed by encapsulating Cypate and AT13387. These nanomicelles exhibited great features, including achieving mutually synergistic PTT/MTT for overcoming thermoresistance and promoting translocation of drugs, increasing the solubility of Cypate and AT13387, showing a pH/redox dual response that contributes to drug release, and having the ability of active targeting. Thus, the nanomicelles developed in this study may be a promising strategy for the precise treatment of TNBC.
Periodontitis is recognized as the major cause of tooth loss in adults, posing an adverse impact on systemic health. In periodontitis, excessive production of reactive oxygen species (ROS) at the inflamed site culminates in periodontal destruction. In this study, a novel ROS-responsive drug delivery system based on polydopamine (PDA) functionalized mesoporous silica nanoparticles was developed for delivering minocycline hydrochloride (MH) to treat periodontitis. The outer PDA layer and the inner MH of the nanoparticles acted as ROS scavengers and anti-inflammatory agents, respectively. Under the synergistic action of PDA and MH, macrophages were polarized from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype. The in vitro experiments provided convincing evidence that PDA could scavenge ROS effectively, and the expression of pro-inflammatory cytokines was attenuated and the secretion of anti-inflammatory cytokines was enhanced through M1 to M2 polarization of macrophages with the cooperation of MH. In addition, the results obtained from the periodontitis rat models demonstrated that the synergetic effect of PDA and MH prevented alveolar bone loss without causing any adverse effect. Taken together, the results from the present investigation provide a new strategy to remodel the inflammatory microenvironment by inducing the polarization of macrophages from M1 toward M2 state for the treatment of periodontitis.
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