Journal of Nanobiotechnology最新文献

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.

Exosomes serve as pivotal nanoscale messengers in intercellular communication by transporting bioactive molecules such as miRNAs, proteins, and lipids that regulate physiological and pathological processes. Emerging evidence highlights exercise as a potent modulator of exosome biogenesis, dynamically altering their release kinetics, molecular cargo, and bioactivity across tissues. Exercise-derived exosomes disseminate systemic adaptations by delivering regulatory signals to noncontractile organs, thereby coordinating multitissue responses that underlie the protective and reparative benefits of physical activity. This review synthesizes current knowledge on the dynamic effects of acute and chronic exercise on exosome profiles and their therapeutic potential in treating neurological, cardiovascular, metabolic, and musculoskeletal disorders. This review further discusses how exosome engineering and precision medicine could harness exosomes as "exercise mimetics," offering cell-free therapeutics for mobility-limited populations. By integrating exercise physiology with translational medicine, this work pioneers a new therapeutic paradigm where exosome-based molecular therapies replicate exercise's multisystem benefits.

Glioblastoma (GBM) is one of the most aggressive malignancies of the central nervous system. Gemcitabine (GEM), a pyrimidine analogue with broad-spectrum anticancer activity, can activate the cGAS-STING pathway and alleviate the immunosuppressive microenvironment of GBM. However, its clinical application is hampered by the formidable challenge of crossing the blood-brain barrier (BBB) and accumulating at the tumor lesion. Herein, a dual-responsive biomimetic nanoprodrug (RMM@GEM NPs) was exploited to enhance the efficient BBB penetration and target cargo delivery by functionalization of glioblastoma cell membranes (MM) camouflaging and further targeting peptide RAP modification. After its selective accumulation at glioma lesion, RMM@GEM NPs accelerates GEM release under the tumor pathological stimuli of reactive oxygen species (ROS) and acidic microenvironment to robustly activate the STING signaling cascades (increased p-STING, p-TBK1, p-IRF3, and p-NF-κB). Simultaneously, cyclodextrin-mediated cholesterol depletion further suppresses PD-L1 expression and alleviates T-cell exhaustion. These findings highlight RMM@GEM NPs as a promising strategy to enhance immune responses in "cold" tumor, providing a potential candidate for efficient and safe immunotherapy in GBM.

A multifunctional liposomal hydrogel nanoplatform (CMH@lip@Res-TCeO₂) was developed for the targeted treatment of psoriasis-like skin inflammation through combined antioxidant and anti-inflammatory mechanisms. The system integrates resveratrol (Res) and mitochondria-targeted cerium oxide nanozymes (TPP-CeO₂) within a thermo-responsive hydrogel matrix, enabling sustained transdermal delivery and enhanced local drug retention. Network pharmacology and transcriptomic analyses identified 36 key targets and highlighted the ROS/mTOR/HIF-1α axis as a critical pathway in neutrophil regulation. Single-cell RNA sequencing revealed fibroblasts, keratinocytes, and neutrophils as key cellular contributors to psoriasis pathogenesis. CMH@lip@Res-TCeO₂ effectively suppressed mitochondrial reactive oxygen species (ROS) accumulation, inhibited mTOR/HIF-1α activation, reduced neutrophil extracellular trap (NET) formation, and alleviated keratinocyte dysfunction. In IMQ-induced psoriasis-like mice, the treatment significantly decreased inflammatory cytokine expression and improved histopathological features. These findings demonstrate that CMH@lip@Res-TCeO₂ exerts multi-level regulation of oxidative stress, metabolism, and inflammation, offering a promising nanotherapeutic strategy for psoriasis and other chronic inflammatory skin disorders.

Kidney stones are among the most common renal diseases with high global incidence and recurrence rates, with calcium oxalate (CaOx) stones constituting 65.9% to 80% of all cases. Minimally invasive surgery remains the primary approach for kidney stones, while limited progress has been made in the drug therapy for CaOx kidney stones over the recent years. The limitations of traditional drug therapy, such as renal toxicity and poor targeting, along with an elusive pathogenesis of CaOx kidney stones, have prevented its widespread clinical application. Renal tubular epithelial cells injury has been reported to play a crucial role in the occurrence and development of CaOx kidney stones. Nanozymes with potent antioxidant and anti-inflammatory properties have the potential to treat CaOx crystal-induced kidney injury. Moreover, as a key stone inhibitor, potassium citrate is widely used to inhibit stone formation due to its ability to modify urinary chemistry. Herein, we designed citrate-coated Prussian blue nanozyme hitchhiking on the neutrophils (NM@CPBzyme) with injured kidney targeting capability and good biosafety. The results showed that NM@CPBzyme alleviated CaOx crystal-induced kidney injury and CaOx crystals deposition. On the one hand, NM@CPBzyme has been demonstrated to not only suppress oxidative stress but also chelate calcium ions, thereby facilitating crystal dissolution. On the other hand, NM@CPBzyme could mitigate neutrophil infiltration, NETosis and inhibit pyroptosis in vitro and in vivo. In addition, RNA sequencing and bioinformatic analysis further showed that NM@CPBzyme ameliorates CaOx crystal-induced kidney injury via oxidative stress and neutrophil mediated inflammatory response. In summary, our results revealed that NM@CPBzyme is a novel strategy for protecting against CaOx crystal-induced kidney injury.

Tumor-derived extracellular vesicles (TEVs) are promising autologous cancer vaccines due to their intrinsic tumor-associated antigens. However, their translation is hindered by immune evasion and the lack of non-invasive tools to monitor vaccination efficacy in vivo. Here, we report a self-reporting nanovaccine engineered by coating TEVs under microfluidics with pH-sensitive manganese dioxide (mTEV). This surface biomineralization on TEVs chemically block inhibitory ligands such as CD47, promoting dendritic cell (DC) uptake and degrades under lysosomal conditions to expose tumor antigens and release Mn²⁺. The released Mn²⁺ activates the cGAS-STING pathway and simultaneously enhances T₁-weighted magnetic resonance imaging (MRI) contrast, enabling visualization of DC trafficking. In ovarian cancer models, mTEVs drove robust DC maturation, antigen presentation, and cytotoxic T cell responses, effectively suppressing tumor growth and peritoneal dissemination. Importantly, early MRI signals in draining lymph nodes correlated with treatment outcomes, providing a non-invasive predictive biomarker of vaccine efficacy. This dual-functional nanovaccine platform integrates immune activation with in vivo tracking, offering a precision strategy for cancer immunotherapy.

Sustainable nanomaterials are emerging as transformative platforms for precision dental medicine, uniquely combining environmental responsibility with individualized therapeutic performance. Green-synthesized metallic, polymeric, carbon-based, and bioactive nanomaterials exhibit superior biocompatibility, biodegradability, and a reduced ecological burden compared to conventionally produced analogues, while enabling enhanced antimicrobial, regenerative, and diagnostic capabilities. This review synthesizes recent advances in eco-friendly nanoparticle synthesis, life-cycle sustainability metrics, and the integration of nanotechnology into patient-specific diagnostics, controlled-release therapeutics, and regenerative dentistry. Emphasis is placed on biogenic routes for silver, gold, ZnO, chitosan, bioactive glass, cellulose nanocrystals, and lignin nanocarriers, as well as their clinical potential in caries management, periodontal regeneration, endodontic disinfection, implant surface engineering, and point-of-care diagnostics. Additionally, their compatibility with multi-omics-driven precision dentistry is highlighted. We further analyze safety profiles, biodegradation pathways, regulatory frameworks, and translational challenges related to standardization and AI-assisted personalization. Sustainable nano-platforms represent a strategic route to advance dental care toward predictive, preventive, and personalized practice while ensuring environmental stewardship and global healthcare equity.