Journal of Nanobiotechnology最新文献

Effective image-guided and precisely controlled drug release remains a critical challenge in cancer therapy, particularly for overcoming drug resistance and minimizing systemic toxicity. Herein, we developed a multifunctional nanoplatform by co-encapsulating a newly engineered near-infrared (NIR)-absorbing semiconducting oligomer (TD19) and doxorubicin (DOX) into DSPE-PEG₅₀₀₀ carriers. Benefiting from a donor-acceptor molecular design, TD19 exhibited a high extinction coefficient, extended π-conjugation, and superior photothermal conversion efficiency, which directly contributed to strong photoacoustic imaging (PAI) and photothermal therapy (PTT) performance. The resulting TD19/DOX nanoparticles (TD19/DOX-NPs) demonstrated dual-responsive drug release triggered by 808 nm laser irradiation and the acidic tumor microenvironment. In vitro, the nanoplatform enhanced cellular uptake, nuclear delivery of DOX, and synergistic apoptosis of breast cancer cells. In vivo, TD19/DOX-NPs achieved precise PAI-guided tumor localization, efficient tumor ablation (96.8% growth inhibition), and no observable acute systemic toxicity in the 4T1 mouse model. This study highlights the structure-function-therapeutic relationship of the designed semiconducting oligomer, linking its rational molecular engineering to chemo-photothermal synergy as a promising nanotheranostic candidate for breast cancer precision therapy.

Background: Neural stem cells (NSCs) transplantation holds promise for intracerebral hemorrhage (ICH) treatment, but its efficacy is limited by poor survival and aberrant differentiation of grafted cells. Here, we demonstrate that exosomes derived from healthy young donor plasma, a natural nanomaterial protect NSCs against pyroptosis, a gasdermin-dependent inflammatory cell death process triggered by ICH.

Methods: Plasma exosomes were extracted from young (Y-exo) and old (O-exo) healthy individuals and characterized. An in vitro model of ICH was established by hemin treatment. For the in vivo study, the mouse ICH model was induced by autologous blood, a combined transplantation of Y-exo and NSCs was then performed as the therapeutic intervention. The protective effects of exosomes on NSCs were assessed via western blotting, immunofluorescence, ELISA, qPCR, and Calcein/PI detection. The therapeutic effects of combined transplantation of Y-exo and NSCs on ICH mice were evaluated through in vivo imaging systems and a series of behavioral tests.

Results: Exosomes derived from young plasma exert protective effects by supporting NSC survival, boosting their proliferative and differentiation capacity in vitro, and ameliorating the peri-hematoma microenvironment in vivo. Strikingly, the efficacy of Y-exo is superior to that of O-exo. Subsequent studies will use Y-exo, in vitro, the Y-exo exerted their protective effects by inhibiting the NLRP3/Caspase-1/GSDMD-mediated pyroptotic pathway and reducing the release of inflammatory cytokines. In vivo, co-transplantation of NSCs and Y-exo enhanced NSCs survival, proliferation, and beneficial differentiation toward neuronal and oliodendroglial lineage while attenuating pyroptosis of NSCs and peri-hematoma tissue. Behavioral tests indicated that mice in the co-transplantation group exhibited superior functional recovery. MiRNA sequencing identified miR-16-5p as a key mediator enriched in Y-exo, which targeted TXNIP to disrupt NLRP3 inflammasome activation. Genetic and pharmacological interventions confirmed that miR-16-5p/TXNIP/NLRP3 signaling pathway is essential for Y-exo's anti-pyroptotic effects.

Conclusions: Our study elucidates a previously unidentified mechanism whereby Y-exo improve neurological outcomes by alleviating the peri-hematoma inflammatory microenvironment, suppressing pyroptosis in transplanted stem cells, and altering their differentiation fate. This study highlights the potential of synergistic strategy to optimize NSCs-based therapy for stroke by combining youth-derived factors, offering new insights into regenerative therapeutics for neurological disorders.

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.