Journal of Nanobiotechnology最新文献

Small extracellular vesicles (sEVs) play a critical role in the progression, diagnosis, and treatment of prostate cancer (PCa), particularly within the tumor microenvironment (TME). Acting as novel biomarkers and agents for targeted biological therapy, sEVs contribute significantly to improving patient survival. These vesicles transport a variety of biomolecules, including proteins, nucleic acids, and lipids, which are instrumental in remodeling the TME, facilitating intercellular communication, and influencing key processes such as tumor growth, metastasis, and therapy resistance. A thorough understanding of sEV heterogeneity, including their biogenesis, characteristics, and potential applications, is essential. Recent advances have illuminated the origins, formation processes, and molecular cargo of PCa-derived sEVs (PCa-sEVs), enhancing our understanding of their role in disease progression. Furthermore, sEVs show promise as diagnostic markers, with potential applications in early detection and prognostic assessment in PCa. Therapeutically, natural and engineered sEVs offer versatile applications, including drug delivery, gene therapy, and immunomodulation, underscoring their potential in PCa management. This review delves into the substantial potential of sEVs in clinical practices for PCa.

With the extensive utilization of plastic products, microplastics/nanoplastics (MPs/NPs) contamination not only poses a global hazard to the environment, but also induces a new threat to the growth development and nutritional quality of plantation agricultural products. This study thoroughly examines the behavior of MPs/NPs, including their sources, entry routes into plants, phytotoxicity under various biotic and abiotic stresses (e.g., salinity, polycyclic aromatic hydrocarbons, heavy metals, antibiotics, plasticizers, nano oxide, naturally occurring organic macromolecular compounds, invasive plants, Botrytis cinerea mycorrhizal fungi.) and controlling strategies. MPs/NPs in agricultural systems mainly originate from mulch, sewage, compost fertilizer, municipal solid waste, pesticide packaging materials, etc. They enter plants through endocytosis, apoplast pathways, crack-entry modes, and leaf stomata, affecting phenotypic, metabolic, enzymatic, and genetic processes such as seed germination, growth metabolism, photosynthesis, oxidative stress and antioxidant defenses, fruit yield and nutrient quality, cytotoxicity and genotoxicity. MPs/NPs can also interact with other environmental stressors, resulting in synergistic, antagonistic, or neutral effects on phytotoxicity. To address these challenges, this review highlights strategies to mitigate MPs/NPs toxicity, including the development of novel green biodegradable plastics, plant extraction and immobilization, exogenous plant growth regulator interventions, porous nanomaterial modulation, biocatalysis and enzymatic degradation. Finally, the study identifies current limitations and future research directions in this critical field.

Traumatic brain injury (TBI) is a leading cause of disability in adults, significantly affecting patients' quality of life. Extracellular vesicles (EVs) derived from human adipose-derived mesenchymal stem cells (hADSCs) have demonstrated therapeutic potential in TBI treatment. However, their limited targeting ability, short half-life, and low bioavailability present significant challenges for clinical application. In this study, we engineered extracellular vesicles (EEVs) by transfecting hADSCs with lentivirus and incorporating ultra-small paramagnetic nanoparticles (USPNs), resulting in EVs with enhanced miRNA expression and targeted delivery capabilities. These EEVs were administered intranasally to specifically target injury sites, effectively modulating the NF-κB signaling pathway to suppress neuroinflammation. In both in vitro and in vivo assessments, EEVs exhibited superior efficacy in promoting neurofunctional recovery and neurogenesis after brain injury compared to unmodified EVs. Furthermore, validation using human brain organoid models confirmed EEVs' remarkable ability to suppress neuroinflammation, offering a promising strategy for TBI treatment.

Sjögren's syndrome (SS) is an autoimmune disease primarily affecting salivary glands, with xerostomia as a distinct clinical manifestation. This disease also poses a significantly increased risk of lymphoma, severely impacting patients' quality of life. The imbalance between Th17 and Treg cells plays a critical role in SS progression, driving severe immune dysregulation, chronic inflammation, and escalating tissue dysfunction. However, current clinical treatments for SS still remain limited, and it continues to be recognized as a refractory disease. Therefore, the development of novel and effective therapeutic strategies is a pressing demand in clinical research. In recent years, extracellular vesicle (EV) therapy has emerged as a promising approach for autoimmune disease treatment, showing encouraging outcomes in modulating immune balance and alleviating symptoms. EVs carry diverse cargo, among which microRNAs (miRNAs) are highly abundant and play critical roles. These small RNAs are essential for EV-mediated functions, particularly in regulating gene expression and modulating the immune microenvironment. Our research team first isolated labial gland mesenchymal stem cells (LGMSCs) and their derived EVs (LGMSC-EVs), which offer potential therapeutic advantages in SS due to their salivary gland origin. Then we screened and identified the highly enriched miRNA let-7f-5p as a key regulator through miRNA profiling analysis. To achieve better therapeutic outcomes, we transfected exogenous miRNA let-7f-5p into LGMSC-EVs to upregulate its expression, thereby constructing let-7f-5p-encapsulated LGMSC-EVs. These modified EVs were subsequently tested in an experimental SS mouse model to evaluate their therapeutic potential. The upregulation of miRNA let-7f-5p in LGMSC-EVs significantly enhanced their therapeutic effects, resulting in clinical improvements such as increased salivary flow and reduced lymphocytic infiltration. Mechanistically, let-7f-5p-encapsulated LGMSC-EVs suppressed Th17 cells by directly targeting the 3'-untranslated region (3'UTR) of RORC, inhibiting the RORC/IL-17A signaling axis, and reducing IL-17A production, thereby restoring Th17/Treg balance and promoting an anti-inflammatory profile. Collectively, this let-7f-5p-encapsulated LGMSC-EV therapy offers a promising target-driven approach for the treatment of SS, achieving improved clinical outcomes and immune rebalance after modification with miRNA let-7f-5p, which presents new potential for the clinical treatment of SS.

Sepsis-induced acute lung injury (ALI) remains a critical clinical challenge with complex inflammatory pathogenesis. While bone marrow mesenchymal stem cells (BMSCs) demonstrate therapeutic potential through anti-inflammatory and cytoprotective effects, their age-related functional decline limits clinical utility. This study developed chitosan-functionalized selenium nanoparticles (SeNPs@CS, 100 nm) to rejuvenate BMSCs through miR-20b-mediated selenoprotein biosynthesis. Mechanistic investigations revealed that SeNPs@CS-treated BMSCs exhibited enhanced mitochondrial transfer capacity, delivering functional mitochondria to damaged alveolar epithelial cells (AECII) for cellular repair. Concurrently, miR-20b upregulation suppressed the RORγt/STAT3/Th17 axis, reducing pro-inflammatory Th17 cell differentiation in CD4⁺ T lymphocytes. The dual-target mechanism integrates immunomodulation via Th17 pathway inhibition with mitochondrial rejuvenation therapy, representing a paradigm-shifting approach for ALI management. These engineered BMSCs mitigated inflammatory markers in murine models, demonstrating superior efficacy to conventional BMSC therapies. Our findings establish SeNPs@CS-modified BMSCs as a novel therapeutic platform combining nanotechnology-enhanced stem cell engineering with precision immunometabolic regulation, providing new avenues for the treatment of sepsis-induced ALI.

Salmonella is one of the most common foodborne pathogens, which can cause severe enteritis and intestinal microbiota imbalance. However, there are limited strategies currently available for preventing or treating Salmonella-induced colitis. Herein, we developed the Cu/Mn-co-doped ZnO tandem nanozyme (ZnO-CM) with pH-responsive multienzyme-mimicking activities via doping engineering for the treatment of Salmonella-induced colitis. Benefiting from the co-doping of Cu and Mn, ZnO-CM nanospheres exhibit remarkable peroxidase-like activity in acidic condition and superoxide dismutase- and catalase-like activities in neutral environment. Animal experiments show that ZnO-CM can efficiently inhibit bacterial growth, alleviate inflammation, and restore the intestinal barrier, resulting in good antibacterial and anti-inflammatory effects on Salmonella-induced colitis. Mechanistically, ZnO-CM functions through inhibiting the continuous accumulation of ROS, increasing the levels of tight junction proteins occludin and claudin-1, and decreasing the expression of pro-inflammatory cytokines IL-1β and IL-6 in intestine. This work not only presents an effective paradigm for Salmonella-induced colitis therapy, but also provides new sights into the prevention and treatment of other bacterial enteritis.

Inflammatory bowel disease (IBD) is characterized by compromised intestinal barrier function and a lack of effective treatments. Probiotics have shown promise in managing IBD due to their ability to modulate the gut microbiota, enhance intestinal barrier function, and exert anti-inflammatory effects. However, the specific mechanisms through which probiotics exert these therapeutic effects in IBD treatment remain poorly understood. Our research revealed a significant reduction of Lactiplantibacillus plantarum (L. plantarum) in the gut microbiota of IBD patients. L. plantarum is a well-known probiotic strain in the list of edible probiotics, recognized for its beneficial effects on gut health, including its ability to strengthen the intestinal barrier and reduce inflammation. We demonstrated that supplementation with L. plantarum could alleviate IBD symptoms in mice, primarily by inhibiting apoptosis in intestinal epithelial cells through L. plantarum's bacterial extracellular vesicles (L. plant-EVs). This protective effect is dependent on the efficient uptake of L. plant-EVs by intestinal cells. Intriguingly, watermelon enhances L. plantarum colonization and L. plant-EVs release, further promoting intestinal barrier repair. Our findings contribute to the understanding of L. plant-EVs in the probiotic-based therapeutic approach for IBD, as they are promising candidates for nanoparticle-based therapeutic methods that are enhanced by natural diets such as watermelon. This study thereby offers a potential breakthrough in the management and treatment of IBD.

Lipid nanoparticles (LNPs) have revolutionized nucleic acid delivery, enabling significant advances in mRNA-based therapeutics. While extensive research has focused on lipid composition, the impact of preparation solutions on LNP performance remains underexplored. This study systematically investigated the effects of pH, salt type, and concentration across key preparation solutions-mRNA aqueous, dilution, exchange, and storage solutions-on the physicochemical properties, stability, and expression efficiency of SM102-based mRNA/LNPs. Findings revealed that the pH of the mRNA aqueous solution was critical, with a pH of 4 optimizing encapsulation efficiency (EE) and cellular expression. The exchange solution's pH significantly influenced biodistribution, particularly liver-specific expression following intravenous and intramuscular administration. Sucrose was identified as essential for freeze-thaw stability, with a 300 mM concentration minimizing aggregation and mRNA leakage. Furthermore, preparation solutions were shown to influence the structural integrity of LNPs, impacting their in vivo and in vitro performance. These insights highlight the importance of preparation conditions in optimizing LNP formulations for clinical applications, offering a foundation for enhanced therapeutic design and delivery.

Inducing ferroptotic cell death has been recognized as a promising approach in cancer therapy. However, ferroptosis can provoke tumor infiltration by myeloid-derived suppressor cells (MDSCs) through HMGB1 secretion, causing a tumor suppressive immune response. On the other hand, ferroptosis also occurs the immune cells due to its non-selective properties, which can compromise anti-tumor immunity. To address these challenges, a two-pronged approach is proposed, encompassing selectively triggered ferroptosis in tumor cells and HMGB1 blockade, aimed at eliciting systemic anti-tumor immunity and alleviating immunosuppression. Herein, GSH-specific driven nanoplatform is composed of uniform FeOOH nanospindles coated with tetrasulfide bond-bridged mesoporous organosilica (DMOS) shell, and loaded with the HMGB1 inhibitor, glycyrrhizic acid (GA). This nanoplatform is endowed with high glutathione (GSH) depletion efficiency and exhibits highly efficient Fe²⁺ and ROS generation capacity, which promotes the accumulation of LPO and subsequently induces ferroptosis. Concurrently, the inhibition of HMGB1 release counteracts the immunosuppressive effects within the tumor microenvironment. This innovative nanoplatform effectively suppresses the growth of 4T1 tumors and notably enhancing the therapeutic outcomes of immune checkpoint blockade across experimental data. The collective findings indicate its potential as a reliable therapeutic strategy for boosting ferroptosis-mediated tumor immunity with favorable safety profiles.

Liver fibrosis is a leading cause of liver-related mortality worldwide, yet effective therapies remain limited. Mesenchymal stem cells (MSCs) have recently shown promise in treating liver fibrosis due to their anti-inflammatory and anti-fibrotic properties. However, the precise molecular mechanisms by which MSCs exert their effects remain unclear. In this study, we explored how human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) contribute to treating liver fibrosis, and revealed a crucial role of ferroptosis in modulating hepatic stellate cells (HSCs) activity. We found that MSCs primarily promote ferroptosis in HSCs in an exosome-dependent manner. Specifically, MSC-derived exosomes (MSC-Exos) deliver miR-499a-5p, which interacts with the transcription factor ETS1, leading to the suppression of GPX4, a key regulator of ferroptosis, thereby reducing the fibrogenic activity of HSCs. Overexpression of ETS1 in HSCs counteracted miR-499a-5p-induced ferroptosis, underscoring the pathway's potential as a target for therapeutic intervention. Furthermore, molecular docking simulations further identified optimal ETS1-GPX4 binding sites. This research uncovers a novel mechanism by which MSCs may treat liver fibrosis, providing insights that could guide the development of more effective therapies for this widespread condition.