Journal of Nanobiotechnology最新文献

Background: Osteoarthritis (OA) is a joint disease with complicated pathophysiologic process, however, the lack of effective therapeutic targets and corresponding pharmaceuticals severely limits treatment options.

Results: Methyl gallate (MG) could delay the pathological changes of OA by reducing cartilage inflammation and degeneration at both cellular and animal levels. Using drug affinity responsive target stability assay and mass spectrometry analysis, we identified HSP90β as a key target of MG in chondrocytes. The interaction between MG and heat shock protein 90β（HSP90β）was further validated by surface-plasmon resonance and cellular thermal shift assay experiments. In OA rat models, a positive correlation between HSP90β and cartilage degeneration was confirmed and upregulated expression of HSP90β and its related pathways was revealed through antibody chip monitoring and KEGG analysis. Moreover, clinical analysis of 53 OA patients showed a positive association between HSP90β expression and pain scores. Conversely, silencing HSP90β in rat chondrocytes significantly reduced the mRNA levels of matrix metalloproteinases and IL-6, and decreased the expression of PI3K/Akt pathway-related proteins. To achieve more effective OA therapy, MG was conjugated to hyaluronic acid (HA) via a reduction-responsive disulfide linker. In an OA mouse model, HA-MG exhibited enhanced therapeutic efficacy compared to free MG, leading to increased accumulation and retention of the conjugate in the joint cavity, as demonstrated by in-situ long-term fluorescence imaging.

Conclusions: This study has identified the important role of HSP90β as a therapeutic target for OA and provided a robust approach to attenuate OA progression using a polysaccharide nanoconjugate.

Bone tumors, encompassing primary sarcomas such as osteosarcoma and secondary skeletal metastases from carcinomas, present a stubborn clinical problem. Their treatment is hampered by three interconnected barriers: the physical impediment of a mineralized matrix that restricts drug access, a profoundly immunosuppressive microenvironment that inactivates antitumor immunity, and the lack of endogenous tissue regeneration following therapeutic intervention. Conventional modalities-including systemic chemotherapy, surgical resection, and even modern immunotherapies-often yield disappointing results against these complex lesions. In this context, nanotechnology offers a fresh therapeutic perspective. Engineered nanoplatforms are designed to home in on bone lesions, disrupt local immunosuppressive networks, and re-establish immunosurveillance. This review critically examines how these integrated systems counteract immune resistance. We focus on platforms that achieve precise bone targeting, reprogram the local immune landscape, and, crucially, coordinate the timing of tumor clearance with the process of functional bone repair. By tackling the dual challenges of immune evasion and structural defects, these multifunctional agents mark a significant departure from conventional approaches, holding the potential to simultaneously eradicate tumors and restore skeletal integrity.

The mRNA-LNP-based SARS-CoV-2 vaccines were a breakthrough for the technology; however, their production requires specialized equipment, and the complex formulation involving four distinct lipid classes imposes stringent requirements on both characterization and quality control. We tested a cationic adjuvant formulation containing a simple two-component liposome formulation based on dimethyldioctadecylammonium bromide and monomycoloyl glycerol-1 (CAF^®04) for mRNA-delivery, which can be complexed with mRNA by simple admixing on-site. The physicochemical characteristics of the resulting vaccine particles depended on the CAF04:mRNA N/P ratio, where an N/P ratio ≤ 1.09 resulted in anionic particles with little aggregation and N/P ratios ≥ 2.18 resulted in increasingly cationic particles that aggregated. These attributes influenced the magnitude of the CD8⁺ T-cell responses induced against OVA-encoding mRNA and at optimal CAF04:mRNA N/P ratios (0.76-1.42), the antigen-specific CD8⁺ T-cell responses reached magnitudes comparable to the DOTMA:DOPE Lipoplex (RNA-LPX) platform. Therapeutic vaccination using CAF04:mRNA delayed tumor growth and enhanced survival in an E.G7-OVA lymphoma model. We present a highly stable mRNA delivery platform that can be freeze-dried for extended storage and admixed with mRNA on-site to induce highly functional CD8⁺ T-cell responses with potential for therapeutic cancer vaccines.

Intracellular bacteria survive are difficult to eradicate by conventional antibiotics. Antimicrobial peptides (AMPs) have garnered increasing attention due to their ability to exert broad-spectrum antibacterial effects through various mechanisms. However, they are also unable to effectively penetrate cell membranes to enter the cytoplasm. Fluorination has been proven to effectively enhance the ability of biopeptides to penetrate cell membranes. We designed a fluoroalkylated Omiganan (PFC-OMN) by conjugating a perfluorocarbon tag to a cysteine-terminated Omiganan (OMN) via a disulfide bond, enabling self-assembly into ~ 59 nm nanoparticles and glutathione-triggered release of active OMN in the cytosol. PFC-OMN retained extracellular activity against S. aureus (MIC = 12.5 µM) and exhibited markedly enhanced intracellular bactericidal potency (IMBC₉₉.₉ = 50 µM vs. > 800 µM for unmodified peptide). FITC-PFC-OMN showed 2.6-4.2× higher cellular uptake and broader cytosolic distribution compared with FITC-C-OMN. PFC-OMN displayed low hemolysis (HC₅₀ ≈ 325 µM) and macrophage cytotoxicity (IC₅₀ ≈ 450 µM). In a murine peritonitis model, PFC-OMN significantly reduced intracellular S. aureus counts. These results indicate that fluoroalkylation can enable AMP-mediated eradication of intracellular pathogens.

Background: Peri-implantitis is driven by persistent multispecies biofilms and a pathological inflammatory microenvironment characterized by elevated reactive oxygen species (ROS), acidic pH, and sustained pro-inflammatory macrophage activation. These coupled features severely limit the efficacy of conventional antimicrobial therapies by restricting drug penetration into mature biofilms and perpetuating immune dysregulation. Therapeutic strategies capable of simultaneously overcoming biofilm mass-transport barriers and restoring immune homeostasis remain lacking.

Results: Herein, we report a microenvironment-responsive nanomotor system (M-CaO₂-CL) that converts pathological inflammatory cues into sustained autonomous motion, enabling active biofilm penetration and concurrent immunomodulation. Triggered by elevated hydrogen peroxide (H₂O₂) and sustained by acidic pH, the nanomotors generate continuous oxygen-driven propulsion, facilitating deep infiltration into dense biofilm matrices and overcoming diffusion-limited transport. This motion-enabled behavior markedly enhances antibacterial efficacy, particularly when combined with mild photothermal treatment under near-infrared irradiation (< 48 °C), achieving efficient biofilm disruption without detectable collateral tissue damage. Beyond antibiofilm activity, the nanomotor platform exhibits intrinsic antioxidant and anti-inflammatory functions, effectively scavenging excessive ROS and reprogramming macrophages from a pro-inflammatory M1 phenotype toward a reparative M2 phenotype. In a rat peri-implantitis model, M-CaO₂-CL treatment significantly reduced bacterial burden, suppressed pro-inflammatory cytokine expression, and preserved peri-implant bone architecture.

Conclusions: Collectively, this study demonstrates a multifunctional nanomotor-based therapeutic strategy that integrates inflammation-responsive propulsion, enhanced biofilm penetration, mild photothermal disinfection, and immune reprogramming. By harnessing pathological microenvironmental cues as endogenous driving forces, the M-CaO₂-CL nanomotor effectively addresses key biological barriers in peri-implantitis, establishing a promising nanotherapeutic platform for biofilm-associated inflammatory diseases.

The treatment of solid tumors with chimeric antigen receptor natural killer (CAR-NK) cell therapy confronts significant barriers, notably poor cellular infiltration and a highly immunosuppressive tumor microenvironment (TME). To overcome these challenges, we developed selenium-containing polymer nanoparticles (ManNAl-SeNPs) loaded with dibenzocyclooctyne (DBCO)-modified mannose. Metabolic glycoengineering metabolic glycoengineering (MGE) enabled efficient labeling of exogenous DBCO on azide (N₃) groups on CAR-NK cells, establishing a bioorthogonal click chemistry targeting strategy, significantly improving the anti-tumor activity of azide-CAR-NK (N₃-CAR-NK) cells, including recognition specificity, migration efficiency, and cytotoxic activity. Herein, ManNAl-SeNPs with ultra-sensitive responsiveness of diselenide bonds, in the acidic TME, diselenide bond releases seleninic acid, acting as an immune checkpoint inhibitor while augmenting CAR-NK cells cytotoxicity. In vivo, the combination of ManNAl-SeNPs with N₃-CAR-NK cells significantly increased targeting capacity and invasiveness. This study presents a TME-responsive nanoplatform with artificial bio-orthogonal combination strategy that effectively enhance the migratory ability and accumulation of CAR-NK cells for potent antitumor therapy.

Oral squamous cell carcinoma (OSCC) remains one of the most aggressive malignancies of the oral epithelium, with limited therapeutic options effectively targeting both tumor growth and metastasis. Plant-derived nanovesicles have emerged as natural, biocompatible nanomedicines with potential applications in cancer therapy. Here, we systematically screened nanovesicles from ten medicinal plants and identified Panax notoginseng-derived nanovesicles (PnNVs) as the most potent inhibitors of OSCC. PnNVs exhibited favorable safety profiles and intrinsic tumor-homing ability, selectively accumulating in orthotopic tongue tumors. In vivo, they markedly suppressed primary tumor growth and lymphatic metastasis. Mechanistically, PnNVs disrupted redox homeostasis by inhibiting the p38-MAPK/NRF2 signaling pathway, thereby inducing ferroptosis, autophagy, and PANoptosis. In addition, PnNVs impaired cancer cell migration by modulating chemokine-associated signaling pathways critical for tumor dissemination. Multi-omic analyses further revealed synergistic contributions of RNA cargos and metabolite components to their multi-target anticancer efficacy. Collectively, our findings establish PnNVs as a natural, multifunctional therapeutic candidate with dual anti-proliferative and anti-metastatic activity, providing a promising preclinical strategy for OSCC treatment.

Obesity, a major global public-health challenge, is a well-established risk factor for numerous metabolic disorders. In this study, we developed a novel nanosystem based on Au clusterzymes (AuCZy) encapsulated in chitosan (CS) and functionalized with an adipose homing peptide (AHP), referred to as AHP-AuCZy@CS nanogel. Specifically, an alternating magnetic field (AMF) was applied to modulate its enzyme-mimicking activity. It was found that AMF stimulation significantly enhanced SOD-like and CAT-like activities, endowing AHP-AuCZy@CS nanogels with superior reactive oxygen species (ROS) scavenging capacity. Furthermore, in vivo experiments demonstrated the efficient targeting of AHP-AuCZy@CS nanogels to white adipose tissue (WAT). After a 45-day treatment regimen (once every three days) with AHP-AuCZy@CS nanogels combined with AMF, obese mice exhibited an 18% reduction in body weight compared to the control group. This combination treatment also suppressed WAT expansion, improved glucose tolerance and insulin sensitivity, and ameliorated lipid metabolic disorders. Mechanistic investigations revealed that AMF-enhanced ROS scavenging by AHP-AuCZy@CS nanogels activated the AMPK signaling pathway, promoting white fat browning and thermogenesis. This work demonstrates the compelling therapeutic potential of clusterzymes combined with AMF for the treatment of obesity and associated metabolic diseases.