Journal of Nanobiotechnology最新文献

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.

Ischemia-reperfusion (I/R) injury is a critical contributor to adverse outcomes following stroke. During I/R injury, excessive production of reactive oxygen species (ROS) leads to various forms of neuronal cell death. Moreover, the blood-brain barrier (BBB) significantly hinders the delivery and efficacy of many neuroprotective agents. Given selenium's crucial role in mitigating brain ischemia, we developed a selenium-based nanozyme encapsulated in glutathione (GSH)-conjugated liposomes to overcome these challenges. Specifically, we encapsulated selenium-doped carbon dot nanozymes (Se-CDs) within GSH-conjugated liposomes (Se-CD@LP-GSH) to enable targeted delivery and enhance therapeutic efficacy in ischemic stroke. This system demonstrates effective ROS scavenging capabilities both in vitro and in vivo, while also enhancing the biocompatibility of Se-CDs and their ability to cross the BBB. In the tMCAo model, Se-CD@LP-GSH reduces the neuronal death and infarct area following cerebral I/R injury, and promotes improvements in spatial learning ability and sensorimotor function. Mechanistically, Se-CD@LP-GSH promoted the upregulation of GPX4, an essential selenoprotein, thereby preserving mitochondrial function and suppressing ROS generation Consequently, the reduced ROS levels inhibit NLRP3/GSDMD-mediated neuronal pyroptosis during cerebral I/R injury. By improving the brain-targeting ability of Se-CDs via GSH-functionalized liposomal delivery, our work elucidates their neuroprotective efficacy and mechanistic basis, thus providing a translationally relevant strategy for ischemic stroke therapy.

Ovarian aging, characterized by declining ovarian reserve, is a pacemaker of aging in the female body. Oxidative stress leads to apoptosis, mitochondrial dysfunction, inflammation, and telomere shortening, accelerating ovarian aging. Scavenging reactive oxygen species (ROS) has been shown to delay ovarian aging; however, there remains a significant lack of antioxidants with both proven efficacy and minimal side effects. DNA tetrahedral nanostructure (DTN) is a promising nucleic acid framework with antioxidant and anti-apoptotic properties. We developed FSH-DTN, a modified nanoparticle equipped with a follicle-stimulating hormone receptor-targeting peptide (FSH33-53) to enhance ovarian accumulation. Compared to native DTN, FSH-DTN showed superior ovarian targeting efficiency as confirmed by in vivo imaging. In both in vivo and in vitro models of acute, subacute, and chronic ovarian aging, FSH-DTN demonstrated superior antioxidant, anti-apoptotic, and anti-aging effects. Further investigation revealed that FSH-DTN can directly eliminate ROS in the ovaries while enhancing ovarian antioxidant capacity by activating the NRF2 signaling pathway, thereby protecting ovarian function. In this study, we offer a new strategy for neutralizing oxidative stress to delay ovarian aging.

Diabetic foot ulcer (DFU) is one of the most serious complications of diabetes and lack effective treatment options. Although platelet-derived growth factor-B (PDGFB) has been approved for the treatment of diabetic wounds, it is difficult to sustainably deliver PDGFB to the wound site of DFU owing to its poor stability and easy degradation. To address these limitations, we developed a lipid nanoparticle (LNP)-encapsulated PDGFB circular RNA (LNP-circPDGFB) formulation designed to achieve sustained local expression and release of PDGFB for enhanced diabetic wound healing. The therapeutic circRNA was synthesized via in vitro transcription (IVT), followed by microfluidic encapsulation into ionizable LNPs to generate LNP-circPDGFB. LNP-circPDGFB facilitated highly efficient and prolonged expression of PDGFB both in vitro and in vivo. It exhibited pleiotropic effects by promoting the proliferation and migration of vascular endothelial cells and fibroblasts, as well as the angiogenesis of vascular endothelial cells. In diabetic mice, a single administration of LNP-circPDGFB could significantly accelerate diabetic wound healing and improved histopathological outcomes without obvious immunogenicity. Single cell RNAseq results also highlighted the potential of LNP-circPDGFB to promote proliferation, migration and extracellular matrix deposition of fibroblasts and vascular repair and angiogenesis of vascular endothelial cells. Taken together, we established LNP-circPDGFB as a promising "single-dose, long-acting" therapeutic platform for DFU treatment, addressing key limitations of current therapies. By leveraging the stability of circRNA and efficient LNP delivery, this approach not only enhances diabetic wound healing but also offers a versatile framework for protein delivery in regenerative medicine.

Background: Tears are an easily accessible biofluid that reflects both emotional states and disease conditions. They are particularly enriched in extracellular vesicles (EVs), which carry proteins and nucleic acids relevant to neurological health. This makes tear EVs a promising source for biomarker discovery. However, limited sample volume and variability pose challenges for identifying reliable biomarkers for clinical diagnosis.

Results: We present AI-driven Biomarker Learning for the Early Diagnosis of Neurodegenerative Diseases (ABLEDx), which applies a conditional variational autoencoder (cVAE) to enhance proteomic analysis of tear EVs. This approach effectively addresses sample limitations and improves the identification of disease-associated biomarkers. Our results reveal that tear EVs capture molecular signals along the eye-brain axis, reflecting contributions from both ocular and central nervous system cells. ABLEDx identified clinically relevant protein modules, which were consistently elevated in patients with neurodegenerative diseases. Moreover, we recognize that KRAS is highly expressed in patients with Alzheimer's disease, Parkinson's disease, and ocular myasthenia gravis, and tear-EV-associated LRG1 and HSPG2 exhibit differentiation between Alzheimer's disease and Parkinson's disease.

Conclusions: ABLEDx demonstrates the utility of combining AI with tear-EV proteomics for non-invasive biomarker discovery. This strategy enables early and real-time detection of neurodegenerative and ocular diseases, offering new opportunities for clinical diagnostics and translational medicine.

Liver Cancer, one of the most lethal cancers in adults, is distinguished by its aggressive invasion, distinctive tumor microenvironment (TME) and resistance to standard treatments, posing challenges. The TME and fibrotic extracellular matrix (ECM) hampers effective drug distribution; hence, new developments in therapeutics have brought creative solutions to these problems. To temporarily breach these barriers and enable targeted treatment, various dynamic therapies using stimuli such as focused Ultrasound, light, chemical reactions, mechanical stress, microwave induction and magnetic fields have demonstrated great promise in inducing localized and spatiotemporal therapeutic effects. This comprehensive review highlights the therapeutic mechanisms, including both chemical and biological effects and elucidates the therapeutic promise of emerging nanomedicine across individual modalities such as sonodynamic therapy (SDT), photodynamic therapy (PDT) and chemodynamic therapy (CDT), supported by preclinical evidence. Thereafter, promising combinatorial dynamic strategies with superior therapeutic effects are outlined. Furthermore, emerging next-generation modalities, including piezodynamic therapy (PZDT), microwave dynamic therapy (MWDT) and magnetodynamic therapy (MDT), with their therapeutic perspectives are discussed in detail. Although these strategies employing emerging nanomedicines have shown remarkable therapeutic potential for clinical translation, controlling physical stimulation and ensuring nanoparticle biocompatibility remain challenging. Continued innovations in medicine and chemistry will be essential for transforming dynamic strategies into clinically viable strategies for liver oncology.

Efficient and uniform delivery of nanomedicine into deep tumors remains challenging due to the limited targeting efficiency and the dense stromal barrier of solid tumors. Here, we report a bacterial biohybrid platform that integrates tumor-tropic bacteria with photoresponsive nanomedicine to achieve deep intratumoral drug delivery through active bacterial locomotion, passive nanoparticle diffusion, and photo-controlled spatiotemporal release. This biohybrid is constructed by conjugating attenuated Salmonella typhimurium VNP20009 with polyglycerol-decorated hollow mesoporous ruthenium nanoparticles, which act simultaneously as photothermal agents and nanocarriers co-encapsulating thermosensitive 1-tetradecanol and chemotherapeutic DOXorubicin. Guided by bacterial chemotaxis, the biohybrid actively colonizes the hypoxic and deep tumor regions inaccessible to conventional nanomedicines. Upon near-infrared irradiation, localized photothermal heating detaches nanoparticles from the bacterial surface, converting transport from active bacterial locomotion to passive interstitial diffusion, and simultaneously melts the thermosensitive 1-tetradecanol to trigger pulsatile doxorubicin release. Following nanoparticle detachment, the unmasked bacterial surface engages with host immune cells, promoting macrophage M1 polarization and establishing a pro‑inflammatory tumor microenvironment. This immune activation acts in concert with photothermal therapy and spatiotemporally controlled chemotherapy to synergistically achieve potent photochemo-immunotherapy with minimal systemic toxicity. Overall, this work establishes a generalizable strategy to achieve adequate intratumoral drug delivery and highlights the therapeutic potential of bacteria-mediated hybrid systems.