Journal of Nanobiotechnology最新文献

Blood-brain barrier (BBB) impermeability remains a major obstacle to the effective treatment of neurological disorders, particularly ischemic stroke. Here, we revealed that plant-derived extracellular vesicle-like nanoparticles (PEVs) offer a promising strategy to overcome this barrier. Using an optimized high-yield extraction protocol, we isolated PEVs from four medicinal plants: Panax ginseng, Panax notoginseng, Gastrodia elata, and Ligusticum chuanxiong. Among these, extracellular vesicles derived from Panax notoginseng (NotoEV, vesicle population) exhibited the strongest neuroprotective effects under hypoxic conditions in vitro and in vivo stroke models. Mechanistically, NotoEV delivered conserved plant microRNAs to recipient neurons, where they suppressed key stress granule nucleators GTPase-activating protein-binding protein 2 (G3bp2), Ubiquitin-associated protein 2 like (Ubap2l), and LSM14A mRNA processing body assembly factor (Lsm14a), activated mammalian target of rapamycin (mTOR) signaling, and promoted mitochondrial stabilization via the B-cell lymphoma 2 (Bcl-2)/ Translocase Of Outer Mitochondrial Membrane 20 (TOM20) axis. This cross-kingdom RNA delivery reprogrammed neuronal stress responses, reduced infarct volume, preserved neuronal morphology, and restored electrophysiological function. Collectively, our findings establish a scalable platform for plant-based nanotherapeutics and highlight the translational potential of NotoEV in treating ischemic stroke.

Real-time and accurate detection of drug-induced liver injury is critical for early intervention and treatment, yet clinically applicable visualization methods remain scarce. Based on the difference in glutathione (GSH) content between the normal liver and the livers with different-grade injury, we report a GSH-activated T₁-weighted magnetic resonance imaging (MRI) nanoprobe (C-MnO), which can be used for non-invasive real-time in vivo magnetic resonance imaging (MRI) of the consumption of GSH in the liver, thereby being applied for the graded diagnosis of liver injury. Due to the presence of abundant disulfide bonds in C-MnO, the T₁ MRI signal around it remained "quenched" until encountering GSH. When C-MnO enters the body and is efficiently absorbed by the liver, it will disassemble and degrade under the action of GSH, thereby activating the T₁ MRI signal. Therefore, this nanoprobe provides an effective visual method for capturing the changes in GSH content during different degrees of liver damages at an early stage, which is beneficial for the graded diagnosis and precision treatment of drug-induced liver injury. Comprehensive in vitro and in vivo studies demonstrate that C-MnO, as a GSH-activated T₁ MRI nanoprobe, enables real-time monitoring and graded diagnosis of drug-induced liver injury, effectively addressing current clinical limitations in the detection of liver injury.

Spinal cord injury (SCI) initiates secondary injury cascades, including ferroptosis and neuroinflammation, which contribute to progressive neuronal and myelin loss. Single-cell RNA sequencing defines a therapeutically actionable window for selenium (Se) replenishment: neuronal and oligodendrocyte selenoproteins-especially Gpx4-show a transient rise at 1-day post-injury followed by sustained suppression with induction of ferroptosis drivers, indicating Se-limited antioxidant collapse. In this study, we extracted a novel Polygonatum-derived fructan and, for the first time, used it to coat selenium nanoparticles, synthesizing PRP@SeNPs via a green, ascorbate-mediated reduction. The PRP coating yields smaller hydrodynamic size, a more negative zeta potential, and a front-loaded yet sustained Se-release profile that aligns with the scRNA-seq-identified supplementation window. In vitro, PRP@SeNPs restore Gpx4 expression, reduce lipid peroxidation, scavenge ROS, and promote M2 microglial polarization. In situ administration in a T-cut SCI mouse model suppresses ferroptosis and glial activation, preserves neuronal and myelin integrity, enhances axonal regeneration, and improves motor function (Basso Mouse Scale, gait analysis, electrophysiology). PRP@SeNPs thus provide a drug-free, biocompatible nanotherapeutic strategy to replenish Se, mitigate secondary injury mechanisms, and promote neuroprotection and remyelination for advanced functional recovery after SCI.

Exosomes are nanoscale extracellular vesicles that transfer proteins, nucleic acids, and lipids, reflecting the state of their parent cells. A persistent scientific challenge is that tumor-derived exosomes (TDEs) facilitate immune evasion, remodel the tumor microenvironment, and create premetastatic niches, intensifying tumor aggressiveness and undermining therapeutic efficacy, ultimately narrowing treatment options to palliative strategies in advanced settings. Yet their dual roles as suppressive agents and potential therapeutic tools remain poorly integrated within current cancer immunotherapy frameworks. This review examines the molecular mechanisms underlying TDE-mediated immune suppression and therapeutic resistance, while also highlighting engineering strategies to exploit or counteract exosome biology. Exosomes derived from chimeric antigen receptor (CAR) T cells preserve antigen specificity and cytotoxic components without the risks of uncontrolled proliferation or cytokine release, offering a safer class of cell free immunotherapies. Advances in genetic engineering, hybrid vesicle design, and nanotechnology have extended exosome applications to the delivery of CRISPR/Cas systems, chemotherapeutic agents, immunoregulatory RNAs, and vaccines, with liposome or nanoparticle integration enhancing targeting and efficacy. Remaining obstacles include the lack of standardized protocols, scalability issues in production, and unresolved regulatory frameworks. Drawing on The Art of War, exosomes can be envisioned as avatars of strategy, discreet messengers capable of undermining host defenses while simultaneously carrying the potential to redirect immunity against the tumor. By embodying both deception and counterattack, they illustrate the capacity to penetrate hidden barriers and redefine the therapeutic battlefield, opening new horizons for precision cancer immunotherapy.

In-stent restenosis (ISR), a chronic vascular proliferative disorder, poses significant clinical challenges due to impaired endothelial repair, suboptimal long-term outcomes of interventional therapies, and complications associated with current preventive strategies. Although gene therapy offers a promising approach for ISR management, its clinical translation is hindered by the scarcity of innovative gene-based drugs and the lack of efficient delivery systems. Here, we identify carbonic anhydrase 1 (CA1) as a potential target in regulating endothelial cell survival, regeneration, and inflammatory responses. We then engineered plant-derived exosome-like nanoparticles (CLENs) to encapsulate CA1-siRNA, enabling targeted delivery and enhanced stability. CLENs (siRNA) exhibit prolonged circulation and precise accumulation at aortic lesions, effectively reducing ISR rates. Mechanistically, this therapeutic approach alleviates endothelial inflammatory activation by suppressing the NF-κB and TNF signaling pathways and downregulating PADI2 expression, while also demonstrating favorable biosafety. Our study presents a novel plant-derived nano-delivery system based on purely natural components for early ISR intervention, which demonstrates both therapeutic efficacy and an absence of adverse effects.

Plant viral co-infections pose a significant threat to global agricultural productivity. In this study, a novel multivalent attenuated vaccine (CMV-R2TP) was developed using the cucumber mosaic virus (CMV) as a backbone, together with a ROS-responsive vaccine nanodelivery system (pCMV-R2TP@PTP-TAT), offering a comprehensive and environmentally friendly strategy for managing plant viruses. Through the modification of the CMV 2b protein, a stable base vector (pR2-2bIII) capable of accommodating up to 400 bp foreign fragments was constructed. The resulting CMV-R2TP vaccine demonstrated protective efficacy ranging from 41.28% to 53.78% against co-infections caused by CMV, TMV, and PVY. To address the constraints of conventional Agrobacterium-mediated delivery, a novel nanodelivery platform, pCMV-R2TP@PTP-TAT, was synthesized through synergistic modification of PLGA with PEI, TK, and TAT. This system demonstrated excellent physicochemical characteristics, achieving 87.1% ROS-responsive release within just 4 h. It was also found to be capable of efficiently delivering nucleic acids into plant cells, resulting in gene expression levels comparable to those achieved by Agrobacterium transformation within 120 h. Notably, the pCMV-R2TP@PTP-TAT system showed exceptional biocompatibility, neither harming plant tissues nor inducing oxidative stress responses. Overall, a comprehensive technical platform was established, integrating multivalent vaccine design, nanodelivery optimization, and safety assessment. This system combines measurable protective efficacy with favorable environmental safety, offering a scalable approach for sustainable management of plant viral diseases and paving the way for novel applications in agricultural nanobiotechnology.

Peptide-drug conjugates (PDCs) offer a powerful therapeutic modality by integrating the targeting specificity of peptides with the cytotoxic efficacy of chemotherapeutics, thereby improving antitumor performance while reducing off-target toxicity. In this study, we engineered biometallic PDCs composed of peptide nanofibers (PNFs), gold nanoparticles (GNPs), and doxorubicin (DOX), termed PGDCs, and incorporated them into photo-responsive dual-network hyaluronic acid hydrogels for combined photothermal and chemotherapeutic (PTT/CT) treatment of breast cancer. The hydrogel was formed by mixing oxidized methacrylated hyaluronic acid (O-HAMA) with PGDCs, followed by rapid photo-crosslinking under 365 nm UV light, achieving gelation within 90 s for localized, on-demand drug deployment. The resulting O-HAMA/PGDC hydrogels exhibited pH-responsive drug release under tumor microenvironments and robust photothermal performance under NIR irradiation. In vitro and in vivo evaluations revealed strong tumor suppression, with 98% inhibition efficiency, effective tumor ablation, and minimal damage to surrounding healthy tissues. The structural modularity of PGDCs-allowing simultaneous integration of metals, peptides, and drugs-opens pathways for designing highly effective, tumor-selective nanotherapeutics with controlled activation, efficient internalization, and combined therapeutic outcomes.

Inflammatory dermatoses like psoriasis and atopic dermatitis are prevalent autoimmune disorders whose management is challenged not only by inflammatory lesions but, more significantly, by persistent pruritus and frequent relapse following treatment discontinuation. The pathogenic progression of these dermatoses is critically influenced by an imbalance between pro-inflammatory adenosine triphosphate (ATP) and anti-inflammatory cyclic adenosine monophosphate (cAMP), alongside reactive oxygen species (ROS) accumulation. To address this imbalance and effectively scavenge ROS, we have developed AC@Mg/Ce-UiO, integrating adenylate cyclase (AC) with a defect-engineered Mg/Ce-UiO nanozyme, for inflammatory dermatosis treatment and recurrence prevention. Mg/Ce-UiO nanozyme, synthesized through a metal-substitution strategy, demonstrates enhanced superoxide dismutase-like and catalase-like activities, facilitating efficient ROS scavenging. Concurrently, the encapsulated AC enzyme catalyzes the conversion of ATP into cAMP. Both in vitro and in vivo studies demonstrate that AC@Mg/Ce-UiO markedly downregulates the expression of inflammatory cytokines and pruritogens, inhibits keratinocyte hyperproliferation, and diminishes the infiltration of immune memory T cells. Consequently, this nanozyme not only alleviates psoriatic symptoms (e.g., lesions and pruritus), but also decreases the likelihood of recurrence. This study introduces a safe and potent dual-catalytic therapy that targets the fundamental pathogenesis of inflammatory dermatoses, providing a promising strategy for achieving long-term remission and preventing recurrence.