Journal of Nanobiotechnology最新文献

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.

Background: Lactobacillus plantarum (L. plantarum) is a probiotic bacterium with diverse health-promoting effects. Recent evidence suggests that these benefits are mediated by extracellular vesicles (EVs) secreted by the bacterium; however, the underlying molecular mechanisms in the context of pathogenic inflammation remain poorly understood.

Results: In this study, we employed super-resolution stochastic optical reconstruction microscopy to elucidate the molecular mechanisms of action of L. plantarum EVs by monitoring alterations in the ultrastructural integrity of cellular organelles in human dermal fibroblasts exposed to Staphylococcus aureus EVs. Pathogenic EV exposure induced characteristic inflammatory changes in organelle morphology. Remarkably, both pre- and post-treatment with L. plantarum EVs restored organelle morphology in a concentration- and time-dependent manner. Cytokine profiling showed selective suppression of interleukin (IL)-6 and IL-8 while preserving IL-10, indicating targeted immunomodulation. We identified nicotinamide adenine dinucleotide (NAD⁺) as a key bioactive cargo, with exogenous NAD⁺ treatment reproducing both structural and cytokine-restorative effects.

Conclusions: These findings establish NAD⁺-mediated organelle protection as a central mechanism through which probiotic EVs mitigate bacterial inflammation. By linking organelle integrity to inflammatory outcomes, our study highlights L. plantarum EVs as nanoscale therapeutic candidates for infection-driven inflammation.

Mesenchymal stromal cell (MSC)-based strategies hold promises for treating diabetic foot ulcers. However, the hostile microenvironment of the lesions characterized by hypoxia, oxidative stress, and chronic inflammation impairs the survival and efficacy of transplanted MSCs. Here, we developed a composite bio-dressing by integrating MSC spheroid (Sp) derived from human embryonic stem cells via trophoblast intermediates (T-MSC) with gelatin methacryloyl hydrogel (Gm) and polydopamine nanoparticles (Pn). The GmPn matrix exhibited excellent adaptability, adhesion, porosity, biodegradability, and biocompatibility. Compared to monolayer-cultured T-MSCs, T-MSC Sp with scalable production via hanging drop demonstrated greater resilience to hypoxia and enhanced the migration and tube formation of vascular endothelial cells by secreting higher levels of chemokines and growth factors, verified by RNA-Seq and cytokine array. Furthermore, the combination of T-MSC Sp with Pn provided superior antioxidant, cell protection, and inflammation-regulatory effects compared to either component alone. The integration of T-MSC Sp, Gm, and Pn resulted in a bio-dressing termed SpGmPn, which accelerated wound area closer compared to Sp alone, owing to the synergistic effects of its components in stage-dependent immunomodulation and enhanced tissue regeneration. Thus, SpGmPn represents a promising and scalable therapeutic strategy for enhancing diabetic wound repair beyond the capabilities of T-MSC Sp alone.

Background: 2E,4E-decadienoic acid (DDA) is an aliphatic compound with potent anti‑oomycete activity against Phytophthora nicotianae (Pn), a plant pathogen responsible for major agricultural losses. Mechanistic studies revealed that DDA targets mitochondria and requires intracellular delivery to exert its activity. To improve its stability and bioavailability, we developed a reactive oxygen species (ROS)-responsive, TAT‑peptide (P) ‑modified liposomal (Lipo) delivery system (DDA@P‑ROS‑Lipo) containing thioketal (TK) linkages that cleave under elevated ROS conditions during pathogen infection, enabling controlled and site‑specific release of DDA. The TAT peptide, as a cell‑penetrating moiety, markedly enhanced intracellular uptake.

Results: The resulting nanoparticles exhibited an average hydrodynamic diameter of approximately 112 nm and a high DDA encapsulation efficiency of 80.84%. They also demonstrated excellent photostability, making the formulation suitable for field application. The nanoscale size and strong affinity for tobacco leaf surfaces reduced the contact angle, thereby improving adherence and deposition. Compared with free DDA, the nanoformulation enhanced mycelial inhibition by 45% and achieved superior control of tobacco black shank disease in pot experiments. Both in vitro cytotoxicity and in vivo zebrafish toxicity assays confirmed the safety of the formulation.

Conclusion: This work presents a simple and effective strategy for the targeted delivery of anti‑oomycete agents. DDA@P‑ROS‑Lipo offers a green and efficient approach for plant disease management under controlled conditions, and future studies will explore its scalability and performance in field environments.

The efficacy of oral chemotherapy for colorectal cancer (CRC) is hampered by poor drug stability and absorption in the upper gastrointestinal tract, as well as inadequate targeting efficiency at tumor sites. To address these issues, we proposed a simple and biocompatible nanogel, which was co-assembled from chemotherapeutic drug 5-fluorouracil (5-FU), regenerated silk fibroin (SF) as a natural protein carrier, and metal ions (Ni²⁺/Cu²⁺). The obtained nanogel system exploited the coordination interactions among 5-FU, amino acid residues, and metal ions to form a multifunctional oral nano-drug system with excellent biocompatibility, high delivery efficiency, and superior tumor penetration capacity. Embedding this nanogel in the chitosan/alginate hydrogel enabled it to effectively traverse the gastrointestinal (GI) tract and accumulate at colorectal tumor sites. Furthermore, the multi-stimuli-responsive properties of SF-based nanogel facilitated tumor microenvironment-responsive drug release, while metal ion-mediated chemodynamic therapy synergistically amplified the chemotherapeutic efficacy of 5-FU. This nanogel system provides a facile and translational strategy for improving the therapeutic performance of CRC chemotherapy.