Journal of Nanobiotechnology最新文献

Impaired dendritic cell (DC) recruitment, maturation, and antigen presentation within the immunosuppressive tumor microenvironment (TME) critically limit the efficacy of cancer immunotherapies. Strategies attempt to restore DC function using systemically administered granulocyte-macrophage colony-stimulating factor (GM-CSF) are constrained by poor tumor accumulation and dose-limiting toxicity. Herein, we developed a biosynthetic, ultrasound-triggered in situ cancer vaccine based on a hybrid nanoplatform (OMVs^GM-Lip@Ce6) that integrates GM-CSF-expressing bacterial outer membrane vesicles (OMVs^GM) with pH/ultrasound-responsive liposomes encapsulating the sonosensitizer chlorin e6 (Ce6). In the acidic TME, the hybrid vesicles destabilize, enabling localized release of biosynthetically loaded GM-CSF. Subsequent local ultrasound irradiation activates Ce6 to generate reactive oxygen species (ROS), inducing immunogenic cell death (ICD) and thereby promoting the in situ release of tumor-associated antigens (TAAs) and damage-associated molecular patterns (DAMPs). These endogenous danger signals, together with pathogen-associated molecular patterns (PAMPs) intrinsically carried by OMVs, synergize with locally delivered GM-CSF to enhance DC recruitment, expansion, and maturation, ultimately facilitating efficient antigen presentation and priming of tumor-specific T-cell responses. This biosynthetic OMVs-based platform thus realizes spatially controlled GM-CSF delivery and self-adjuvanted in situ cancer vaccination, effectively remodeling the immunosuppressive TME and eliciting robust systemic antitumor immunity to overcome resistance to immunotherapy.

The oral mucosa, as an important barrier to external exposure, is susceptible to damage caused by various factors, leading to a series of clinical symptoms. Traditional treatment methods have problems such as short drug retention time and unstable local exposure, which make it difficult to meet the treatment needs of oral mucosal injuries. Biomaterials-based drug delivery system can significantly improve the local residence time, permeability and bioavailability of drugs through ultra-small particle size, surface modification and controllable release characteristics, and provide precise targeted therapy. This paper summarizes the application of biomaterials-based drug delivery system in oral mucosal injury, and analyzes its advantages in multi-stage collaborative treatment, including prevention of disease, effective treatment and promotion of rehabilitation. Although the current biomaterials-based system has made some progress in improving treatment effect and patient compliance, it still faces challenges such as long-term safety and manufacturing differences. In the future, biomaterials-based drug delivery system is expected to become an important tool for the treatment of oral mucosal diseases and play an important role in clinical practice.

Developing redox nanozymes able to disrupt cellular homeostasis and promoting immunotherapy offers great potentials to develop highly efficient cancer therapy, but remains challenging. Herein, we initially proposed a high entropy-based layered double hydroxide (LDH) nanosheets (denoted as HE-NS) regulation strategy to achieve high yields of reactive oxygen species (ROS), breaking relatively vulnerable homeostasis, remodeling the tumor microenvironment (TME), further trigger cell pyroptosis. Specifically, compared with low entropy and medium entropy LDH, this unique HE-NS exhibits better multienzyme catalytic activity, which can be further enhanced under ultrasound (US) irradiation. Density functional theory (DFT) calculations confirm that this superior performance can be attributed to the multi-element environment in HE-NS, which optimally modulates the electronic structure of the Fe active site. This modulation yields an intermediate hydrogen peroxide (H₂O₂) adsorption strength, thereby significantly reducing the energy barrier for superior peroxidase (POD)-like activity. The HE-NS can significantly induce pyroptosis, which further eliciting an adaptive immune response, leading to immunogenic cell death (ICD). The reprogramming of the immunosuppressive TME by HE-NS has been confirmed by both in vitro and in vivo studies. This study proposed a new strategy of ultrasound-enhanced pyroptosis-mediated immunotherapy, which effectively enhanced the therapeutic effect.

Ulcerative colitis (UC) is an inflammatory bowel disease that significantly impacts patients' quality of life. The pathogenesis of UC remains incompletely understood, with oxidative stress and inflammation emerging as novel research targets. This study first isolated Flos Sophorae immaturus exosome-like nanovesicles (FSIEVs), demonstrating high purity, uniform particle size, and excellent biocompatibility and biosafety, with potential for treating UC. In vivo, FSIEVs improve the overall condition of a dextran sodium sulfate-induced murine model of UC, reduce intestinal inflammation and oxidative stress, and repair intestinal barrier integrity. Moreover, FSIEVs exhibit anti-UC effects by modulating the gut microbiota (enhancing Lactobacillus species), promoting tryptophan metabolism, and increasing the production of indole-3-acetic acid (IAA). Findings from antibiotic treatment, fecal microbiota transplantation (FMT), and intestinal organoid models confirmed that IAA is a key metabolite mediating the anti-UC effects of FSIEVs, and all these approaches significantly activated the aryl hydrocarbon receptor (AhR). The role of AhR in the anti-UC effects of FSIEVs was further validated using AhR antagonists. Notably, FSIEVs alleviated UC symptoms involving the enrichment of beneficial anti-UC Lactobacillus species, L. paracasei by mono-colonization. In summary, FSIEVs improve UC by regulating the gut microbiota and tryptophan metabolites, enhancing IAA production, activating AhR, and suppressing NLRP3 inflammasome activation and ROS production.

Background: Radiation-induced proctitis is a common complication of radiotherapy for pelvic malignancies, for which effective local treatments remain limited. Epigallocatechin gallate (EGCG) has antioxidant and anti-inflammatory activities but is limited by poor stability and bioavailability. This study aimed to develop a stable, rectally deliverable EGCG-based formulation to mitigate radiation-induced rectal injury.

Results: An EGCG-zinc (EGCG-Zn) nanocomplex was prepared via metal-polyphenol coordination and formulated into a thermosensitive rectal suppository for localized delivery. Zinc coordination significantly improved EGCG stability while preserving its antioxidant activity. The suppository enabled prolonged rectal residence and enhanced local drug exposure. In irradiated mouse models, EGCG-Zn suppositories reduced oxidative stress, DNA damage, and inflammatory responses in rectal tissue, and promoted epithelial regeneration and tight junction restoration. Transcriptomic and molecular analyses suggested involvement of inflammation-related and epithelial barrier-associated signaling pathways. No detectable local or systemic toxicity was observed after repeated administration.

Conclusions: These findings indicate that an EGCG-Zn-based thermosensitive rectal suppository is a safe and effective localized strategy for alleviating radiation-induced proctitis, with potential translational value for the management of radiation-associated rectal injury.

The reconstruction of large bone defects remains a significant clinical challenge, primarily owing to the insufficient mitochondrial protection and osteogenic activity of conventional implants. Exosomes (EXOs) derived from mesenchymal stem cells have emerged as promising tools for bone repair. This study reports a mitochondria-targeted therapeutic strategy utilizing EXOs derived from bone marrow mesenchymal stem cells (BMSCs). On MitoQ incorporation, these EXOs (EXO-MitoQ, EM) exhibit the targeted scavenging of mitochondrial reactive oxygen species; moreover, on surface decoration with the nucleic acid aptamer Apt 19 S (EM-Apt), they show the enhanced recruitment and precise delivery of BMSCs. The engineered EXOs show robust BMSC-targeting specificity and mitochondrial protective efficacy. To optimize their regenerative microenvironment and biomechanical properties further, these functionalized EXOs are integrated onto a 3D-printed β-tricalcium phosphate scaffold coated with a small intestinal submucosa (SIS) hydrogel, forming a composite system (TCP/SIS@EM-Apt). In a rat calvarial defect model, this TCP/SIS@EM-Apt scaffold increased the BV/TV by 1.9-fold compared to TCP/SIS, due to the combination of multiple multifunctional therapeutic effects (anti-inflammatory, angiogenic, and osteogenic). The mitochondria-targeting strategy proposed in this study presents a promising solution for the reconstruction of large bone defects and offers a synergistic approach for addressing complex regenerative challenges.

Effective osseointegration requires successful interaction between an implant and the local bone and immune environments. Surface modification presents a promising strategy to enhance the biocompatibility and integration of titanium implants. Although emerging research on transition metal carbides and nitrides (MXenes) demonstrates their potential to improve implant integration by modulating macrophage behavior and osteogenesis, existing studies have not explored synergistic modification strategies or the specific molecular mechanisms linking immunomodulation to bone healing. To address this, we developed a novel alkali-etched MXene (AE-MXene) coating by integrating alkali etching with MXene nanosheet loading, creating a platform that simultaneously optimizes micro/nanoscale surface topography and bioactive functionality-a synergistic approach previously unreported for MXene-based implants. Through comprehensive in vitro and in vivo analyses, we demonstrate that the AE-MXene surface possesses potent antibacterial, anti-inflammatory, and pro-osteogenic properties. Notably, we reveal for the first time that AE-MXene activates the AMP-activated protein kinase (AMPK)-mechanistic target of rapamycin (mTOR) pathway in macrophages, significantly upregulating autophagy to drive enhanced osteogenesis and angiogenesis. These findings delineate a unique autophagy-mediated mechanism through which AE-MXene promotes osseointegration, distinguishing it from prior MXene implant studies and highlighting its therapeutic potential for immunomodulatory and antimicrobial applications.