Journal of Nanobiotechnology最新文献

Infectious wounds induce a cycle of bacterial proliferation, oxidative stress accumulation, and dysregulated macrophage polarization, collectively hindering tissue repair. Conventional wound dressings typically address these pathological factors in isolation, resulting in suboptimal therapeutic outcomes. Here, we report the design of a biocompatible multifunctional hydrogel (GAPC). This system integrates self-assembled Proanthocyanidin/Chlorhexidine nanoparticles into a dual-network GelMA/ADM scaffold. Consequently, the hydrogel exhibits simultaneous antibacterial activity, ROS scavenging, and immunomodulatory capacity. In vitro, GAPC hydrogel has superb antibacterial, antioxidant, and anti-inflammatory effects. On the other hand, GAPC hydrogel promotes M1-to-M2 macrophage transition and preserved cellular viability under oxidative stress. Furthermore, in vivo it accelerated infected burn wound closure, enhanced collagen remodeling, and stimulated neovascularization. Collectively, GAPC hydrogel interrupts the "infection-oxidative stress-inflammation" loop, offering a safe and promising option for managing infected wounds.

The CRISPR/Cas system has become an indispensable tool for programmable and accurate biosensing, with its performance critically dependent on precise activity control. While most regulatory strategies have focused on engineering Cas proteins or modifying CRISPR RNAs, relatively little attention has been given to the design of substrate probes. Here, we systematically characterize the trans-cleavage activity of split CRISPR/Cas12a on structured substrates and leverage this insight to engineer a tunable "Hooded" probe with switchable properties. This probe architecture confers protection against trans-cleavage, and its activity can be progressively modulated by varying the probe length. Utilizing this design, we constructed a multiplexed logic-gated detection platform for direct and simultaneous analysis of miRNA and PSA, which demonstrated high sensitivity and specificity. Furthermore, we validated the robust performance of this system for logic-operated imaging in diverse cellular models, confirming its reliability in complex biological settings. Overall, our Hooded probe strategy not only broadens the applicability of CRISPR/Cas12a in molecular diagnostics, but also provides a novel design principle for the multiplexed biosensing.

This study explored the molecular mechanisms by which T7 peptide-modified liposomal irisin (T7@Lipo@Irisin) alleviates perioperative neurocognitive disorders (PND) via regulation of the AMPK/PGC-1α metabolic pathway. T7@Lipo@Irisin nanoparticles were prepared by thin-film hydration and ultrasonic dispersion and showed favorable physicochemical performance, with an encapsulation efficiency of approximately 85%. Serum analysis of healthy donors (n = 10) and PND patients (n = 6) showed higher IL-6 and TNF-α and lower brain-derived neurotrophic factor (BDNF) in PND. In vitro, T7@Lipo@Irisin restored mitochondrial membrane potential, reduced reactive oxygen species (ROS) accumulation, enhanced Neuro-2a hippocampal neuron viability, and activated the AMPK/PGC-1α axis under oxidative stress. In a PND mouse model, it improved Garcia neurological scores, preserved neuronal morphology, and decreased apoptosis. Multi-omic integration of scATAC-seq/scRNA-seq and TMT-based proteomics demonstrated enhanced neuro-glial crosstalk, epigenetic activation of metabolic/antioxidant genes (e.g., Sirt1, Nfe2l2), and upregulated pathways (mitochondrial function, NAD-dependent metabolism, synaptic homeostasis). Proteomics confirmed upregulation of SIRT1, NDUFS2, and BDNF, forming a network linked to energy metabolism and neural repair. Collectively, T7@Lipo@Irisin mitigates PND by activating AMPK/PGC-1α to enhance mitochondrial function and stabilize the neuro-microenvironment.

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.