Journal of Nanobiotechnology最新文献

To address the severe side effects of radiotherapy, high recurrence and metastasis rates, and the limited efficacy of single-mode phototherapy in treating nasopharyngeal carcinoma (NPC), this study reports the development of dumbbell-shaped composite optical nanoprobes enabling multimodal optical imaging-guided NIR-II photothermal-catalytic-immuno synergistic therapy. The nanoprobes consist of platinum nanocluster (PtNCs)-tipped gold nanorods (AuNRs) with surface-loaded indocyanine green (ICG) and NPC-targeting peptides (APINs), that exhibit excellent NIR-II absorption properties, photothermal conversion efficiency, and photoacoustic imaging capability. Moreover, the plasmonic resonance effect of AuNRs enhances the catalytic activity of PtNCs at both ends of the AuNR, promoting the generation of reactive oxygen species and thereby synergistically inducing tumor cell destruction. The APINs can be efficiently internalized by NPC cells, present superior biocompatibility, and effectively induce cell killing under 1064 nm laser irradiation. Further in vivo experiments validate the NPC-targeting multimodal imaging capability and tumor inhibition is achieved post treatments, accompanied by the induction of immunogenic cell death. At 18 days post-administration, NPC-xenografted tumor recurrence and metastasis are significantly suppressed. This approach offers a new optical therapeutic model for precise NPC theranostics, with potential clinical application values.

Bimodal imaging tracers that combine nuclear and optical modalities are gaining increasing relevance for in vivo applications in oncology, particularly for surgical guidance, where both real-time visualization and preoperative deep-tissue localization are crucial. Nanobodies are heavy-chain antibody fragments that offer unique advantages in this context, such as high specificity and rapid clearance, which allows for precise tumor localization and real-time surgical navigation. In this systematic review, we evaluate research studies reporting nanobody-based tracers for dual-modality imaging and analyze their design strategies, preclinical imaging performance, and translational progress. The analyses revealed that molecular targets commonly overexpressed in cancer cells, such as HER2, EGFR, and CEA have been the primary focus in the design of these tracers, together with widely used fluorophores like Cy5 and IRDye800CW combined with radionuclides such as gallium-68, technetium-99m, and copper-64. The preclinical performance of the reported tracers was highly promising, both in absolute tumor uptake and ability to achieve high-contrast images rapidly, as highlighted by a CD38-targeting tracer that produced a ~ 96-fold tumor-to-muscle ratio within hours of injection. While achieving stable and site-specific dual labeling remains a technical challenge, the combination of high target specificity and rapid background clearance makes nanobody-based systems particularly well-suited for generating high-contrast images on the same day of administration. This positions nanobodies as a versatile platform to develop tracers that enhance real-time image-guided surgery in oncology and ultimately improve patient outcomes.

Within the complex landscape of the tumor microenvironment(TME), extracellular vesicles(EVs) function as sophisticated nanoscale signaling hubs that govern the intercellular crosstalk driving metastatic progression and immune modulation. Despite their burgeoning potential as next-generation biomarkers and biocompatible nanocarriers, the clinical translation of EVs is currently impeded by an incomplete elucidation of their complex spatiotemporal kinetics in vivo. This review provides a critical synthesis of the EV pipeline, from microenvironment-modulated biogenesis to advanced theranostic applications. We begin by analyzing how specific microenvironmental cues, such as hypoxia, acidosis, and radiation, modulate the cargo and surface markers of EVs to reveal new opportunities for bioengineering. Subsequently, we critically evaluate current isolation strategies and, more importantly, label-based and label-free imaging modalities, comparing their resolution and sensitivity for tracking EV biodistribution in real-time. Finally, we discuss the integration of these imaging technologies with therapeutic strategies, highlighting the transition of EVs from biological entities to engineered nanomedicines for liquid biopsy and targeted delivery. By identifying current technical bottlenecks in quantification and off-target labeling, we propose an integrated roadmap to accelerate the clinical translation of EV-based cancer nanotheranostics.

Vitiligo pathogenesis involves progressive melanocyte loss and keratinocyte dysfunction, which are driven primarily by oxidative stress resulting from excessive ROS accumulation. We engineered a temporally controlled hydrogel microneedle system that integrates ginseng-derived exosomes (G-Exos) with biomimetic polydopamine nanoparticles (PDA@PEGs) to concurrently target the pathogenic triad of vitiligo, including oxidative stress, inflammation, and melanocyte deficiency. This system employs methacrylated hyaluronic acid (HAMA) hydrogel microneedles for rapid PDA@PEG release while utilizing glyceryl monostearate micelles to achieve matrix metalloproteinase-9 (MMP-9)-responsive G-Exo release at inflammatory foci, enabling intelligent spatiotemporal control. Functionally, G-Exos help restore redox homeostasis and suppress inflammation through bioactive constituents, thereby protecting melanocytes and enhancing keratinocyte proliferation. Moreover, PDA@PEG promotes repigmentation through the dual mechanisms of exogenous melanin deposition and endogenous melanogenesis stimulation. In murine models, this strategy achieves significant repigmentation within 3 weeks by activating follicular stem cells, upregulating melanogenic markers (Tyr/Mc1r), increasing antioxidant defense (ApoE), and suppressing inflammatory signaling (IL-17). This natural-biomimetic hybrid design leverages biocompatible materials to co-target multiple pathological axes, offering a novel self-adaptive approach for microenvironmental rehabilitation in vitiligo.

The rising demand for ultrasensitive, field-deployable detection technologies has intensified interest in nanoprobe-based monitoring of environmental contaminants. Fomesafen (FSA), a widely used post-emergence agricultural herbicide, poses significant ecological and health risks due to its slow degradation and prolonged environmental persistence. Addressing the need for rapid in situ detection, we propose a novel turn-on fluorescent nanoprobe (RBO) that combines small-molecule self-assembly, target-triggered disassembly, and adaptive signal amplification to achieve highly sensitive and quantitative detection of FSA. This "immediate-response" system exhibits exceptional performance, including high selectivity, sub-minute response time (< 1 min), high sensitivity (LOD = 0.39 µM), and a dual fluorescent-colorimetric readout that enhances detection reliability. Field applications demonstrate that the nanoprobe supports diverse use cases, enabling on-site quantification of FSA on food surfaces and in soil, as well as real-time visualization and localization of FSA in plant tissues and zebrafish models for accurate assessment of pesticide-induced crop damage and ecological risk. Additionally, RBO has been adapted into test strips and hydrogel-based portable sensors and integrated with smartphone-imaging workflows, substantially improving on-site detection efficiency and device miniaturization. Collectively, this nanoprobe offers a powerful and reliable platform for monitoring FSA across agricultural, environmental, and biological matrices.

Bacterial infections rank as the second leading cause of death globally, driven primarily by the alarming rise of multidrug-resistant (MDR) pathogens. These pathogens severely undermine the efficacy of conventional antibiotics and pose a grave threat to modern medical practice. To counter this urgent crisis, engineered metal nanozymes have emerged as a promising alternative therapeutic strategy. Leveraging their intrinsic enzyme-mimetic catalytic activity to generate bactericidal reactive oxygen species (ROS), metal nanozymes achieve potent broad-spectrum antibacterial action while minimizing the risk of resistance development. Beyond core ROS generation, these nanozymes employ sophisticated complementary mechanisms, including bioactive ion release and stimuli-responsive dual functionality. This multifaceted approach enables simultaneous pathogen eradication and protection of host tissue. Such unique therapeutic attributes, combined with high stability, persistent catalytic activity, favorable biocompatibility, precise tunability, and the potential for synergistic catalytic cascades, establish metal nanozymes as compelling candidates for next-generation antibacterial therapies. This review comprehensively summarizes the fundamental catalytic mechanisms underlying their antibacterial action and details advanced rational design strategies to optimize nanozyme performance. Furthermore, diverse metal-based nanozyme platforms for combating bacterial infections are classified and analyzed, highlighting recent advances in synergistic combination therapies that amplify therapeutic outcomes. Finally, we critically address persistent translational challenges and propose feasible strategies to advance these innovative platforms toward safe and effective clinical deployment against resistant infections.

The widespread use of plastic products has led to a serious environmental problem, with nanoplastics ubiquitously contaminating the environment and sustaining human exposure, yet the impacts of nanoplastics on human health remain poorly understood. In this study, based on preliminary epidemiological investigations, we found that abnormal pain perception exists in populations chronically exposed to manufacturing environments that mainly produce polystyrene plastics. Further mechanistic studies demonstrated that high-dose polystyrene nanoparticles (PS NPs) induce pain hypersensitivity and elucidated their molecular underpinnings. Upon high-dose PS NPs exposure, microglia in the spinal dorsal horn internalized a fraction of the PS NPs, which were subsequently found to bind to mitogen-activated-protein-kinases (MAPK) pathway components (ERK, JNK, and p38). Molecular dynamics simulations further suggested that this binding could induce conformational alterations in the MAPK components, potentially enhancing the flexibility of their phosphorylation sites (Thr-X-Tyr) and thereby facilitating activation by upstream kinases. As a canonical inflammatory and pain-associated pathway, MAPK activation elevates neuroinflammatory cascades in the spinal dorsal horn, driving neuronal hyperexcitability and, consequently, pain hypersensitivity. Notably, the PS NPs-induced hypersensitivity was reversed by microglial depletion (PLX5622) and inhibition of the MAPK pathway. Collectively, our findings delineate PS NPs-triggered sensory pathophysiology and establish a proof-of-concept mechanistic nexus between environmental pollutants and aberrant somatosensation.

Background: Periodontitis is a chronic inflammatory disease characterized by excessive oxidative stress, persistent bacterial biofilms, and progressive destruction of periodontal tissues. Current clinical treatments primarily focus on controlling bacterial infection but often show limited long-term efficacy due to unresolved immune dysregulation. Therefore, therapeutic strategies that simultaneously target microbial biofilms and the pathological immune microenvironment are urgently needed. In this study, we developed an injectable dual-drug hydrogel incorporating curcumin (CUR) and glycyrrhizic acid (GL) for the treatment of periodontitis.

Methods: CUR was dissolved in melted polyethylene glycol distearate and then dispersed in an aqueous medium to form micelles (CURM). Compared to CUR, CURM exhibited improved solubility and stability, thereby displaying greatly enhanced antioxidative, anti-inflammatory, and antibacterial activities. CURM were subsequently embedded within a hydrogel self-assembled from glycyrrhizic acid and polyvinyl alcohol (GLH) to form a dual-drug hydrogel system (CURM@GLH). Experimental periodontitis was established in mice to test their in vivo effects.

Results: Owing to the intrinsic anti-inflammatory and antioxidative properties of glycyrrhizic acid, the hydrogel exhibited combined effects in regulating immune dysregulation. The CURM@GLH effectively protected cells from oxidative damage, reduced intracellular reactive oxygen species levels, promoted macrophage polarization from the proinflammatory M1 phenotype toward the pro-regenerative M2 phenotype, and downregulated proinflammatory cytokine expression. In a ligature-induced rat model of periodontitis, local administration of the hydrogel significantly alleviated periodontal oxidative stress and inflammation and markedly reduced alveolar bone resorption.

Conclusions: This study presents an injectable dual-drug hydrogel, CURM@GLH, that integrates biofilm inhibition with immunomodulatory regulation, offering a promising host-directed therapeutic strategy for periodontitis. The proposed approach provides new insights into the design of multifunctional biomaterials for the treatment of chronic inflammatory diseases associated with biofilm persistence and immune imbalance.