Journal of Nanobiotechnology最新文献

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.

The advancement of nanotechnology has revolutionized reproductive healthcare worldwide. It has enabled the treatment of various conditions, such as infertility, endometriosis, ectopic pregnancies, erectile dysfunction, sexually transmitted infections (STIs), and reproductive tissue cancers. Nanotechnology offers improved imaging, personalized drug administration, and early diagnosis, leading to more accurate treatment outcomes. It can enhance fertility preservation, improve individualized therapy, and improve diagnostic methods. Additionally, nanotechnology-powered drug delivery systems increase effectiveness while reducing side effects. Clinical trials utilizing nanoparticles for cellular treatments, targeted drug delivery, early infection detection, reproductive system malignancies and precise medication delivery are currently underway. Nanotechnology has opened new possibilities in areas such as disease detection, drug administration, diagnostic imaging, and cancer treatment. This review aims to provide an overview of the different types, characteristics, and synthesis methods of nanocarriers designed for medication delivery in the context of reproductive disorders and diseases. It seeks to enhance the understanding of the current state of the art and explore potential future advancements in this field.

Silk fibroin scaffolds (SFCs) that exploit piezoelectricity for osteochondral repair have been hampered by both insufficient electromechanical output and a pro‑inflammatory joint microenvironment that erodes therapeutic efficacy. To overcome these barriers, we developed an intra‑articular implantable scaffold with enhanced piezoelectricity, called FENS@MF, via covalently integrating ultradispersible magnetic nanoparticles (MNPs) into SFCs via EDC/NHS crosslinking. Under magnetically controlled stimulation, FENS@MF generates an ~ 8.5‑fold increase in output voltage, a threefold enhancement in tensile strength, and undergoes only 15.65% degradation by protease XIV over 15 d, thereby sustaining potent electromechanical signaling. In vitro, it markedly upregulates chondrogenic (COL2, SOX9), osteogenic (RUNX2, BMP2), and angiogenic (VEGF, eNOS) markers, while inducing M1‑to‑M2 macrophage polarization to attenuate inflammation. In rat osteochondral defect models, FENS@MF outperforms conventional SFC and FENS scaffolds, achieving cartilage and subchondral bone regeneration with bone mineral density and trabecular thickness comparable to autologous grafts. FENS@MF enhances the piezoelectric effect by responding to the magnetic field (MF) and absorbing electromagnetic waves, and cooperates with magnetic stimulation and immune microenvironment regulation to achieve efficient osteochondral regeneration. Enhanced piezoelectric signals may drive SOX9-mediated chondrogenesis through activation of p38 MAPK phosphorylation (upregulation of COL2/ACAN) and trigger osteogenic differentiation through β-catenin nuclear translocation (upregulation of RUNX/BMP2).This study is the first to integrate the piezoelectric effect, magnetic stimulation and immunomodulation, which breaks through the limitation of a single functional scaffold, establishes a 'structure-function-signal' paradigm for intelligent osteochondral repair, and provides a multifunctional platform for functional tissue regeneration.

Nanoparticles traverse the blood-brain barrier (BBB) through passive diffusion and vesicular transcytosis, but the quantitative contributions of these routes remain difficult to determine. Here, we combine a controlled in-vitro human BBB model (hCMEC/D3 Transwells) with a physics-informed neural network (PINN) to interpret transport kinetics and estimate paracellular and vesicular components. Monodisperse polystyrene nanoparticles (20, 50 and 120 nm) showed low polydispersity, stable ζ-potential and minimal cytotoxicity. Intact monolayers displayed high TEER and low tracer permeability, whereas TNF-α induced reversible junctional opening. Apical-to-basolateral transport increased with junctional loosening and remained size-dependent; clathrin and dynamin inhibition reduced flux without altering TEER or tracer passage. A mass-balance-constrained PINN incorporating a TEER-linked permeability term reproduced transport profiles and generalized to combined perturbation (TNF-α + chlorpromazine). Under our conditions, the model suggested that vesicular uptake represented the major route, with a smaller diffusion component that increased during junctional disruption and clathrin inhibition. Overall, this combined experimental-computational approach provides a practical framework for pathway-informed evaluation of nanoparticle transport across the BBB.

Periodontitis is a localized inflammatory condition triggered by periodontal pathogens and marked by uneven loss of alveolar bone. The clash between the persistent inflammatory environment and requirement for bone regeneration complicates the treatment of periodontitis. To address this issue, we developed a core-shell microneedles drug delivery system responsive to both high matrix metalloproteinase (MMP) expression and a local acidic microenvironment, which are the pathological characteristics of periodontal lesions. This system utilizes a dual mechanism of MMP hydrolysis and pH triggering to achieve precise spatiotemporal release of therapeutic molecules and multimodal synergistic treatment. The microneedles system utilizes a layered core-shell design: the outer shell is loaded with glycyrrhizic-acid-functionalized MIL-101, which encapsulates the core layer containing mesenchymal stem cell-derived exosomes. In the initial treatment phase, when MMP levels are elevated and pH is low, the system rapidly releases drug-loaded nanoparticles from the microneedle shell, thereby significantly inhibiting the pro-inflammatory cytokine storm and alleviating excessive oxidative stress. Subsequently, exosomes released from the microneedles core in a sustained manner contribute to rebalancing the immune microenvironment and inducing new bone formation within periodontal defects. This novel drug delivery strategy combines precise drug delivery, immune regulation, and tissue regeneration of periodontitis-associated bone defects by integrating pathological microenvironmental responsiveness, thereby overcoming the challenge of graded drug release in the complex oral environment and providing an innovative therapeutic paradigm for clinical treatment.

Diabetes-induced osteoporosis significantly elevates the risk of fracture-related disability and mortality. Developing effective therapeutic strategies for diabetic-related bone defects has become a pressing concern in both clinical and research domains. This study innovatively constructs a near-infrared light-responsive (NIR) intelligent hydrogel system (carboxymethyl chitosan/gelatin/black phosphorus@bFGF, CG/BPb), utilizing carboxymethyl chitosan and gelatin as the matrix while integrating polydopamine (PDA)-functionalized black phosphorus nanosheets (BP@PDA) as a controlled-release carrier for basic fibroblast growth factor (bFGF). The CG/BPb hydrogel demonstrated remarkable mechanical strength (up to 25 kPa compressive stress at 55% strain) and antioxidant capacity, scavenging 81.1% of ROS and 83.3% of hydroxyl radicals. Under NIR irradiation (1 W/cm², 5 min), the hydrogel achieved a stable photothermal temperature of 42 ± 1 °C, enabling controlled release of bFGF (60% cumulative release within 20 min at pH 6.5) and phosphate ions. In vitro, assessments revealed that the hydrogel enhanced osteoblast viability by 85% in scratch assays and upregulated osteogenic genes (ALP, Runx2, and OCN). Additionally, it also promoted M2 macrophage polarization (increased CD206, decreased iNOS) and suppressed osteoclast activity via NFATc1 and MAPK pathways. In vivo, in a diabetic rat calvarial defect model, the CG/BPb + NIR group showed significant bone regeneration, with increases in bone volume fraction (BV/TV) and bone mineral density (BMD), alongside enhanced vascularization (elevated CD31/CD34/α-SMA expression). This innovative strategy, grounded in material design and synergistic biological functions, not only provides a new solution for the treatment of diabetic bone defects but also promotes technological progress in the field of bone tissue engineering, with substantial academic value and practical applications.

Low back pain (LBP) is a widespread global health concern that profoundly impairs patients' quality of life and productivity. Intervertebral disc degeneration (IVDD) is considered a major pathological factor in low back pain, yet the underlying mechanisms of IVDD remain incompletely understood. Current treatment strategies primarily focus on symptomatic relief through medication or surgical removal of degenerated tissue, lacking effective interventions that can reverse the degenerative process. This study investigates the role of fatty acid metabolism in IVDD and proposes a novel therapeutic strategy. Through single-cell sequencing and multi-omics analysis of clinical samples, we identified ACOT13 as a key regulator of fatty acid metabolism. We demonstrated that under pathological conditions, ACOT13 inhibits the AMPK/ACC signaling pathway, leading to disrupted fatty acid metabolism, mitochondrial dysfunction, and subsequently, pyroptosis, which accelerates IVDD progression. Furthermore, we developed an innovative self-assembled nanoparticles based on a traditional Chinese medicine formula. Employing molecular dynamics simulations, we elucidate the self-assembly mechanism, identifying the core constituents and establishing the key roles of hydrophobic interactions, π-π stacking, and hydrogen bonding as the driving forces. Moreover, we revealed that this nano-formulation suppresses ACOT13 function, activates the AMPK/ACC pathway, and improves fatty acid metabolism and mitochondrial function, thereby suppressing pyroptosis and ultimately alleviating IVDD progression. In summary, this study explores a novel mechanism of IVDD from the perspective of fatty acid metabolism and identifies key active components (N-QJZG) from a traditional Chinese medicine decoction, providing new insights for IVDD treatment and promoting the modernization of traditional Chinese medicine research.

Fungal infections, particularly intractable cases such as fungal keratitis (FK) and skin wound infections, remain a pressing global health challenge, further exacerbated by rising antifungal resistance and treatment-associated cytotoxicity. Herein, we report a highly effective, non-antibiotic therapeutic strategy integrating reactive oxygen species (ROS) generation and cuproptosis via ZnO₂ cores wrapped with a TA-Cu metal-phenolic network shell (ZnCu@TA) to combat fungi. Upon anchoring to fungal cell walls, ZnCu@TA responds to acidic microenvironments by releasing H₂O₂ and Zn²⁺ from the ZnO₂ core, thereby creates a concentrated burst of ROS that directly damages the cell wall, while promoting copper uptake to induce cuproptosis through mitochondrial dysfunction, leading to effective eradication of Candida albicans and biofilm disruption. In models of FK and skin wound infection, ZnCu@TA significantly reduced pathogens and inflammation with no observed adverse effects, and demonstrated promising preservation of visual function. These findings highlight ZnCu@TA as a safe and effective antifungal nanoplatform for treating superficial fungal infections, offering potential for clinical translation.

As a classic nanozyme, titanium dioxide (TiO₂) is increasingly utilized in medical fields such as anti-infection, tumor therapy, and inflammation regulation. However, their expanding application has raised concerns regarding biosafety, particularly their potential threat to maternal and fetal health. To evaluate this risk, this study established a pregnant rat model, focusing on the placenta as a potential target organ, to investigate the developmental toxicity and potential interventions associated with the use of TiO₂ nanozymes (TiO₂ NZs) as therapeutic agents during pregnancy. The results revealed that gestational intake of TiO₂ NZs led to fetal growth restriction, abnormal placental weight increase, and induced placental energy metabolism disruption along with excessive autophagy activation. Surprisingly, when attempting to reverse these toxic effects, we found that TiO₂ NZs suppressed AMPK expression, prompting Compound C and phenformin to unconventionally regulate energy imbalance-induced autophagy via non-AMPK/mTOR pathway-dependent mechanisms. This resulted in a complex scenario where the two drugs produced inverted effects-"aggravation" vs. "alleviation"-during intervention. These findings indicate that despite the significant medical value of TiO₂ as a nanozyme, they pose non-negligible safety risks, and pharmacological interventions may trigger unexpected effects. Therefore, while advancing their clinical application, it is crucial to prioritize in-depth mechanistic studies and the development of precise intervention strategies, especially ensuring the long-term health and safety for maternal and fetal populations.