Journal of Nanobiotechnology最新文献

A multifunctional liposomal hydrogel nanoplatform (CMH@lip@Res-TCeO₂) was developed for the targeted treatment of psoriasis-like skin inflammation through combined antioxidant and anti-inflammatory mechanisms. The system integrates resveratrol (Res) and mitochondria-targeted cerium oxide nanozymes (TPP-CeO₂) within a thermo-responsive hydrogel matrix, enabling sustained transdermal delivery and enhanced local drug retention. Network pharmacology and transcriptomic analyses identified 36 key targets and highlighted the ROS/mTOR/HIF-1α axis as a critical pathway in neutrophil regulation. Single-cell RNA sequencing revealed fibroblasts, keratinocytes, and neutrophils as key cellular contributors to psoriasis pathogenesis. CMH@lip@Res-TCeO₂ effectively suppressed mitochondrial reactive oxygen species (ROS) accumulation, inhibited mTOR/HIF-1α activation, reduced neutrophil extracellular trap (NET) formation, and alleviated keratinocyte dysfunction. In IMQ-induced psoriasis-like mice, the treatment significantly decreased inflammatory cytokine expression and improved histopathological features. These findings demonstrate that CMH@lip@Res-TCeO₂ exerts multi-level regulation of oxidative stress, metabolism, and inflammation, offering a promising nanotherapeutic strategy for psoriasis and other chronic inflammatory skin disorders.

Kidney stones are among the most common renal diseases with high global incidence and recurrence rates, with calcium oxalate (CaOx) stones constituting 65.9% to 80% of all cases. Minimally invasive surgery remains the primary approach for kidney stones, while limited progress has been made in the drug therapy for CaOx kidney stones over the recent years. The limitations of traditional drug therapy, such as renal toxicity and poor targeting, along with an elusive pathogenesis of CaOx kidney stones, have prevented its widespread clinical application. Renal tubular epithelial cells injury has been reported to play a crucial role in the occurrence and development of CaOx kidney stones. Nanozymes with potent antioxidant and anti-inflammatory properties have the potential to treat CaOx crystal-induced kidney injury. Moreover, as a key stone inhibitor, potassium citrate is widely used to inhibit stone formation due to its ability to modify urinary chemistry. Herein, we designed citrate-coated Prussian blue nanozyme hitchhiking on the neutrophils (NM@CPBzyme) with injured kidney targeting capability and good biosafety. The results showed that NM@CPBzyme alleviated CaOx crystal-induced kidney injury and CaOx crystals deposition. On the one hand, NM@CPBzyme has been demonstrated to not only suppress oxidative stress but also chelate calcium ions, thereby facilitating crystal dissolution. On the other hand, NM@CPBzyme could mitigate neutrophil infiltration, NETosis and inhibit pyroptosis in vitro and in vivo. In addition, RNA sequencing and bioinformatic analysis further showed that NM@CPBzyme ameliorates CaOx crystal-induced kidney injury via oxidative stress and neutrophil mediated inflammatory response. In summary, our results revealed that NM@CPBzyme is a novel strategy for protecting against CaOx crystal-induced kidney injury.

Tumor-derived extracellular vesicles (TEVs) are promising autologous cancer vaccines due to their intrinsic tumor-associated antigens. However, their translation is hindered by immune evasion and the lack of non-invasive tools to monitor vaccination efficacy in vivo. Here, we report a self-reporting nanovaccine engineered by coating TEVs under microfluidics with pH-sensitive manganese dioxide (mTEV). This surface biomineralization on TEVs chemically block inhibitory ligands such as CD47, promoting dendritic cell (DC) uptake and degrades under lysosomal conditions to expose tumor antigens and release Mn²⁺. The released Mn²⁺ activates the cGAS-STING pathway and simultaneously enhances T₁-weighted magnetic resonance imaging (MRI) contrast, enabling visualization of DC trafficking. In ovarian cancer models, mTEVs drove robust DC maturation, antigen presentation, and cytotoxic T cell responses, effectively suppressing tumor growth and peritoneal dissemination. Importantly, early MRI signals in draining lymph nodes correlated with treatment outcomes, providing a non-invasive predictive biomarker of vaccine efficacy. This dual-functional nanovaccine platform integrates immune activation with in vivo tracking, offering a precision strategy for cancer immunotherapy.

Sustainable nanomaterials are emerging as transformative platforms for precision dental medicine, uniquely combining environmental responsibility with individualized therapeutic performance. Green-synthesized metallic, polymeric, carbon-based, and bioactive nanomaterials exhibit superior biocompatibility, biodegradability, and a reduced ecological burden compared to conventionally produced analogues, while enabling enhanced antimicrobial, regenerative, and diagnostic capabilities. This review synthesizes recent advances in eco-friendly nanoparticle synthesis, life-cycle sustainability metrics, and the integration of nanotechnology into patient-specific diagnostics, controlled-release therapeutics, and regenerative dentistry. Emphasis is placed on biogenic routes for silver, gold, ZnO, chitosan, bioactive glass, cellulose nanocrystals, and lignin nanocarriers, as well as their clinical potential in caries management, periodontal regeneration, endodontic disinfection, implant surface engineering, and point-of-care diagnostics. Additionally, their compatibility with multi-omics-driven precision dentistry is highlighted. We further analyze safety profiles, biodegradation pathways, regulatory frameworks, and translational challenges related to standardization and AI-assisted personalization. Sustainable nano-platforms represent a strategic route to advance dental care toward predictive, preventive, and personalized practice while ensuring environmental stewardship and global healthcare equity.

Background: Chronic obstructive pulmonary disease (COPD) frequently coexists with extrapulmonary comorbidities, most notably cardiovascular diseases (CVD). However, the mechanisms linking COPD to CVD, particularly atherosclerotic CVD, remain poorly understood. Extracellular vesicles (EVs), as key mediators of inter-organ communication, may participate in this pathological connection. This study aims to determine whether EVs derived from airway epithelial cells (AECs) of individuals with COPD contribute to endothelial dysfunction and atherosclerosis.

Methods: EVs were isolated from primary airway epithelial cells of COPD patients and matched controls. Their effects on endothelial cell function were assessed in vitro by evaluating inflammation, apoptosis, and monocyte adhesion. ApoE-/- mice were intravenously injected with these EVs to examine their impact on atherosclerotic lesion development. Differentially expressed microRNAs were identified, and the regulatory relationship between miR-141-3p and PDCD4 was validated through molecular assays. Additionally, miR-141-3p supplementation was performed to determine its therapeutic potential in mitigating endothelial injury and atherosclerosis.

Results: COPD AECs-derived EVs markedly increased endothelial inflammation, apoptosis, and monocyte adhesion compared with control EVs. In ApoE-/- mice, COPD-derived EVs accelerated the formation of atherosclerotic plaques. Mechanistic analyses revealed that miR-141-3p was significantly downregulated in COPD EVs and directly targeted the 3' untranslated region of PDCD4 to regulate its transcription, leading to dysregulation of PDCD4/NF-κB signaling in endothelial cells. Restoration of miR-141-3p levels in COPD-derived EVs alleviated endothelial injury and reduced atherosclerotic lesion progression both in vitro and in vivo.

Conclusions: This study identifies a previously unrecognized mechanism by which COPD AECs-derived EVs may promote atherosclerotic CVD via miR-141-3p-mediated regulation of PDCD4 and subsequent activation of NF-κB signaling. These findings highlight miR-141-3p as a promising therapeutic target to reduce vascular complications in COPD.

Macrophage-driven oxidative stress and chronic inflammation play pivotal roles in the progression of atherosclerosis. Given the overactivation of poly (ADP-ribose) polymerase (PARP) in atherosclerosis, PARP inhibitors have potential therapeutic potential, but their efficacy is limited due to poor in vivo targeting. Platelet-rich plasma-derived extracellular vesicles (PEVs), which inherently target inflammatory sites and mitigate oxidative stress, offer a promising delivery platform. Here, we developed NGPPEVs, a nanoplatform that employs PEVs to deliver niraparib, a PARP inhibitor, followed by encapsulation of Ca(HCO₃)₂ to generate gas within cells, thereby combining targeted therapy with ultrasound imaging capabilities. In vitro, NGPPEVs significantly scavenged intracellular reactive oxygen species (ROS) and suppressed pathways related to oxidative stress and cholesterol metabolism. Mechanistically, NGPPEVs suppressed foam cell formation by inhibiting the PARP1-IL-6-CD36 axis, leading to significant downregulation of the key scavenger receptor CD36. In apolipoprotein E-deficient mice fed a high-fat high-cholesterol diet, NGPPEVs demonstrated superior therapeutic efficacy, effectively reducing atherosclerotic plaque area and enhancing plaque stability. Collectively, NGPPEVs have great potential in the precise diagnosis and treatment of atherosclerosis.

Oxidative stress and mitochondrial dysfunction are major barriers to the healing of diabetic wounds (DW). Eliminating reactive oxygen species (ROS) and restoring mitochondrial function are considered effective strategies to accelerate DW healing. Although extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) have shown therapeutic potential, the quality and yield of mitochondrial components in naturally secreted EVs are limited. Thus, we employed a top-down approach, using the self-assembly properties of membrane components to develop artificial nanovesicles enriched with mitochondria-associated proteins derived from human umbilical cord MSCs. These cell-derived nanovesicles (CNVs) selectively encapsulate mitochondrial proteins, effectively reducing intracellular ROS levels and specifically restoring mitochondrial membrane potential (∆Ψm) and morphology. Furthermore, the CNVs demonstrate remarkable antioxidant and mitochondrial functional restoration capacity, involving the restoration of mitochondrial complexes I, Ⅲ, V and the uncoupling process, as well as multiple mitochondrial function-associated pathways, such as the ALDH2/HADHA/HADHB axis, the IDH2/GSR/GSH axis, and the Ca²⁺/VDAC1 axis. In vivo experiments further validated the therapeutic potential of CNVs, which significantly promoted wound healing in diabetic mice. In conclusion, our study emphasizes the potential of artificial nanovesicles containing organelle-associated proteins in DW therapy, providing a novel and promising strategy for organelle-based disease treatment.

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.